August 15, 2023 • 35 mins
Lab Rat Chat - Episode 34 with Dr. Ben Wylie
Get ready to embark on a fascinating scientific journey with our esteemed guest, Dr. Ben Wylie. We know you're curious about his career journey, his cutting-edge work in sarcoma research, and his innovative approach towards cancer treatment. So, we promise you an enlightening conversation that is sure to feed your curiosity and inspire your scientific spirit.
In the first part of our conversation, Dr. Wylie takes us through his journey, from his childhood fascination with the natural world to his current role in cancer research at the Telethon Kids Institute. He opens up about his career transitions, his love for academic research, and the critical work his team is doing in pediatric sarcoma to utilize a biodegradable material to deliver immunotherapy during surgery. This approach, which targets invisible micrometastatic disease left behind during surgery, could potentially transform the landscape of post-surgical cancer treatment.
The conversation takes an exciting turn towards veterinary research and the canine clinical trials to test the efficacy of their immunotherapy gel in dogs diagnosed with sarcoma. We discuss what hopes to be very promising results from this trial and how it can hopefully be translated into the human world. Stay tuned, and prepare for a thought-provoking ride into the world of scientific innovation.
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Resources & Links:
- A surgically optimized intraoperative poly(I:C)-releasing hydrogel prevents cancer recurrence - PubMed (nih.gov)
- Sarcoma Translational Research | Telethon Kids Institute
- World-first clinical trial in Perth could lead to breakthrough treatment for children with sarcoma - ABC News
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Transcript
Episode Transcript
Available transcripts are automatically generated. Complete accuracy is not guaranteed.
Speaker 1 (00:05):
This podcast is supported by Americans for
Medical Progress and was foundedand created through the Michael
D Hare Fellowship, awardedannually to support projects
that inform and educate thepublic about the critical role
of animal research in furtheringmedical progress.
The Fellowship honors the lateDr Michael Hare, a renowned
board-certified laboratoryanimal veterinarian who
dedicated his career toscientific and medical
(00:25):
advancements and who was deeplycommitted to animal welfare and
advocacy.
We've got Dr Wiley with ustoday.
He's going to talk to us aboutsome sarcoma research some
(00:45):
really cool stuff they're doingthere.
As part of our promotion ofJuly is in the US, new A's
National Sarcoma Awareness Month.
He's going to give us somereally good information about
what sarcoma is, some of theresearch they're doing there.
Now let him tell you all aboutthat.
But before we get started, I dojust want to tell everybody out
there to please go on socialmedia rate review our show, make
(01:09):
comments on our posts, followus on Instagram.
If you're listening to this, onSpotify, apple iTunes the great
thing is this is not live.
You have the opportunity topress pause.
Rate review the podcast.
It really helps our exposure.
More people can find us, morepeople can hear us, more people
can find out about what Librachat's all about.
So thank you for everyone fordoing that.
(01:29):
We've noticed more and morefollowers lately, and I think
it's all because of ourdedicated listeners out there.
So thank you for that.
And with that, let's go aheadand get into today's episode.
So, dr Wiley, if you will justtell us a little bit about your
background, what made you sointerested in research and
science, and just give us alittle description of the
journey to get where you're atin your career today, Thanks,
(01:50):
jeff, and of course, thanks forhaving me on the podcast.
Speaker 2 (01:52):
It's fantastic.
I think the work you guys aredoing you know, telling everyone
about the awesome researchthat's going on and all the
animal work that we're doing isreally important.
So I think most people'sjourney into research and
certainly my journey starts withcuriosity.
It's probably the key aspect ofyou know what drives people's
desire for research, and it'sreally that wanting to
(02:12):
understand why and how thingswork.
And for me that really startedoff early on in my life in
thinking and looking at thenatural world.
So I was really interested inanimals documentaries and I
actually wanted to be aveterinarian at a very early
sort of young age.
Didn't quite get the grades todo that straight out of school,
so I chose actually to go touniversity and study biomedical
science and from there that'sreally where my research
(02:34):
interest sort of was firstpiqued and the research journey
began.
I think the real likerevelation for me came in
finding a topic that I wasreally interested in and that
was, you know, a third yearuniversity.
You know that I taught inimmunology and learning all
about the immune system, howeverything worked, all the
things that were going on insidemy body.
That was really fascinating.
And at the same time I did aresearch project over the summer
(02:57):
break at uni and I worked in alab that was focused on the
genetics of wheat fungus, whichI thought was really pretty
boring, but I knew I likedworking in the lab.
That showed me I liked workingin the lab.
So from there I had this ideathat's where I wanted to end up
doing research.
It took looking around for youknow, a few different jobs to
find a place where I couldreally apply that for immunology
(03:17):
in an area that I felt couldhave a real positive impact, and
that ended up being in cancerresearch.
And so, you know, I had acouple of research assistant
jobs where I learned a lot ofskills and that really led me on
to, you know, my PhD, which wasat the telecom kids institute,
working in the cancer center,and there I was looking at
specific immune cells calleddendritic cells and they have a
(03:38):
role in your body which is todetect cancer and other things
like viruses and bacteria and toactivate your immune system to
destroy those pathogens.
And really when I was startingmy PhD, we were just sort of
learning that your immune systemcan be activated to destroy
those cancer cells, and thefirst research was coming out of
labs in America showing thatthere was real potential in
using this as a therapy forcancer patients.
(04:00):
So my career path didn'tnecessarily always take that
straight line, like you mightthink.
There have been times where Iwasn't certain what my research
future was going to hold.
After my PhD I took a bit of aleft turn.
I took a job at a local drugdiscovery company and I worked
there for a couple of yearsdeveloping a range of different
therapies across different areas, and that gave me a really good
look at, you know, thecommercial side of research,
(04:21):
which is really focused onpushing a drug candidate to the
clinic, and that was kind ofrefreshing because it wasn't
something I'd done during my PhD.
My PhD research had been verysort of fundamental, but some
people call basic research aboutyou know how the cells of your
immune system function andinteract with cancer, so that
was really interesting.
However, I still felt that pullfrom you know academic research
, like I still had somethingleft to do, something unfinished
(04:42):
there, and so when the chancecame to sort of move back to
Telethon kids with a new groupthat was starting up there, I
jumped right in and I haven'tlooked back.
And that group is the sarcomagroup.
They're looking at developingnew, safer and more effective
ways to treat pediatric sarcomaand help kids who have this
terrible cancer.
Speaker 1 (04:59):
Yeah, that's awesome.
It seems like it's a cancer thatdoes affect, unfortunately, a
lot of children.
I can definitely relate to alittle bit of your journey about
not having the greats to getinto vet school.
I didn't have a right out ofundergrad and out of getting my
master's degree and ended up aseveryone that listens to this
show knows, because I say itover and over is I had a 10 year
gap between graduate, myundergrad, until applying to vet
(05:21):
school and really I didn't havethese huge intentions of going
to vet school right away and itwas something that my career
within the field of biomedicalresearch led me to wanting to go
to vet school.
But had I tried to apply to vetschool right out of undergrad?
There's no way, and so I wasable to kind of build up my
resume by showing all thisexperience with animals and in
that way.
So I'm thankful for my journeyand no one really has that
(05:42):
straight path to get to wherethey are, and I think that's
what makes everyone's story sointeresting and it's always cool
to hear everyone's story andbackground, so appreciate that.
Speaker 2 (05:51):
It's funny I'll touch on it a little bit later but I
actually almost converted overto vet school during my
undergrad degree and one of thereasons that I thought I'm not
really sure about vet school isbecause I wasn't sure how I
would handle having to dosurgery on animals.
And I guess as I'll touch on abit later you know, in my
current project that's actuallyone of the things I've gone back
to and a skill that I'velearned.
So it's funny how these thingscome around.
Speaker 1 (06:10):
Yeah, absolutely so, all right.
Well, since July, let's say, Iknow it was actually August 4th,
so for everyone listening, wedidn't get this out in July, but
July that was our intention.
Scheduling can be difficultwhen we're halfway across the
world.
July is our coma healthawareness month.
So let's first you've alreadytalked about it a little bit
what exactly is sarcoma, youknow?
Just give us some background onthat, as much information as
(06:33):
you can about you know how manypeople might be living with it.
Is it aggressive, nonaggressive, that sort of thing.
Speaker 2 (06:39):
So sarcomas are really a group of cancers.
We kind of linked them all inunder this one name of sarcoma.
But they're generally solidcancers that form in the
connective tissues of your body.
So these can be things like inthe muscle, in the fat around
nerves and just generally in theconnective tissue that holds
your body together.
Sarcomas are actuallyreasonably rare in adults.
They're actually much morecommon in kids.
(07:00):
They're the third most commoncancer, behind blood cancer and
cancer in kids, although overall, thankfully, childhood cancers
are actually very rare incomparison to cancer in adults.
So I think in the US the totalis about 15,000 people a year
diagnosed with sarcoma and abouta thousand of those will be
kids.
At the Telethon Kids Institute,where I work, we're really
focused.
We're a kids research institute, we're focused on pediatric
(07:23):
oncology and pediatric cancersand for kids sarcoma is a very
serious disease.
One in three kids still diefrom sarcoma, despite our best
efforts and the best currenttherapies that we have.
And indeed sarcomas can be quitelocally aggressive and because
they're a solo cancer, the mainsort of first intervention that
an oncologist will normallyprescribe is a surgery to remove
(07:44):
a lump.
So anecdotally, we hear thesestories of kids.
Actually, you know they'll havea bit of a lump somewhere on
their body.
It's actually quite interesting.
Often they'll have like asporting mishap or an injury, or
they'll fall over and bumptheir leg and they'll say, oh,
that really hurts.
And they'll tell their parentsthat they've got this bump.
That hurts and it just doesn'tseem to get better over time,
and then so that results in atrip to the doctor and, you know
(08:05):
, a biopsy or something of thislump, and then often it turns
out to be a sarcoma.
We call this a solo cancer.
It's a lump.
It can be removed surgicallyand that's generally the first
treatment that is prescribed.
The oncologist or the surgeonwill go in.
They'll do a surgery to try andremove all of the sarcoma, if
they can.
Often because sarcoma isinvolved in connective tissue,
so around the, around the organsinvolved with nerves, it's
(08:27):
often not possible to remove allof that cancer in one go, and
so this is one of the mainproblems with sarcoma.
They're quite locally invasiveand aggressive, and because
surgeries aren't alwayseffective, it means that the
patients have to have follow up,chemo and radiotherapy.
It's also quite interesting.
We do interact with both adultsurgeons and then the pediatric
surgeons at the hospital thatwe're located in in Perth and
(08:50):
the kind of surgeries thatthey'll do are also quite
different.
So the kind of surgery that youmight apply, the surgical
approach that you might apply inan adult is very different than
in a pediatric patient as well,where they there's a real
preference not to do, you know,major surgery, not to limb
removal surgery and things likethat, because obviously that's
going to massively affect apediatric patient or a child's
(09:10):
ongoing wellbeing and state oflife throughout the rest of
their life, even if they arecured of their sarcoma.
It's really on us in theresearch side to start coming up
with better therapies that canhelp these kids with sarcoma.
That's what our lab is allabout.
We say it telephone kids and inthe cancer center we're all
about developing safer andkinder therapies for kids.
Speaker 1 (09:28):
So in like in dogs for example, osteosarcoma is a
really big one.
Is that pretty common inchildren also?
Is it more soft tissue?
Speaker 2 (09:36):
The three big ones in kids are osteosarcomas, and
then there are a couple of softtissue sarcomas which we're sort
of interested in particularly,and then another group which are
called rabdomyosarcomas, andthese are the ones that form in
the muscles Interesting in kids.
They all affect slightlydifferent age groups as well, so
some will affect very youngkids, some will really affect
the kids as they're becomingadolescents and young adults.
(09:56):
So turning into teenagers andyoung adults, there's a
crossover there in theclinicians and how they're
treated when they're sort oftransitioning through that phase
from being an older kid to ayoung adult, to a full adult,
and that can affect the kind ofcancer treatment that they
receive.
Speaker 1 (10:10):
Yeah, absolutely, and I guess the success rate on
their treatment is going todepend on many variables, such
as how early they catch it, howinvasive it already is, whether
or not it's already spread andthat sort of thing.
Speaker 2 (10:21):
Yeah, of course.
Speaker 1 (10:23):
So yeah, since you already talked about some of
those treatment options outthere, just tell us a little bit
specifically about your team'sresearch and that novel type of
I believe you guys are doingsome immunotherapy delivery and
a unique system.
So how'd you guys come up withthat idea and then talk to us a
little bit about some of thoseresults so far?
Speaker 2 (10:42):
Yeah, sure, I mean I'll touch on the current kind
of state of play, I guess,because it's important to know
that there's a lot of researchthat's gone on over the last 30
to 50 years for cancer patientsaround chemotherapy and
radiotherapy.
The number of people survivingthese cancers is, you know,
we've done really the best thatwe can, but for sarcoma in
particular and in pediatricpatients, the state of play
(11:02):
hasn't really changed for maybe10 or 15 years.
They haven't been those steadyimprovements anymore with those
kind of traditional therapiesand that's why we're really
focused on immunotherapy.
The other reason that I thinkthe whole of the Telephone Kids
Cancer Center, where I work, isreally focused on immunotherapy
is we know that chemotherapy andradiotherapy they do require
high doses of treatment.
There can be toxicitiesassociated with these treatments
(11:24):
and in kids particularly, thesecan be long-term developmental
side effects that can really goon and affect the kids after for
a long period of time, evenafter they're cured of their
cancer.
So immunotherapy for usrepresents a way to, you know,
potentially increase the ratesof people that were curing of
cancer, while also reducingthose side effects that we see
from chemotherapy andradiotherapy.
(11:45):
And that's really, I guess,where this whole project was
born from Anecdotally my PI,who's the head of the lab that I
work in.
He began his life as anoncologist before moving
completely to the research field, so he was so in love with
research he sort of saw the needfor research being so strong
that he completely jumped overto the research world and now is
100% focused on cancer research.
(12:07):
He was actually working withorthopedic surgeons at a certain
time while working with sarcomapatients in his oncology clinic
, and that interaction sort ofled him to this idea.
In orthopedics, often whenthey're doing something like a
hip replacement, they'll placesomething in that wound site
which is either coated orembedded with antibiotics to try
and prevent infection aftersurgery, and so that sort of
(12:29):
sparked our idea is to well, ifwe can use a material to deliver
antibiotics during surgery, whynot a material that we can
actually deliver immunotherapyduring surgery as well?
And this really sort of becameup with this concept of surgery
being this window of opportunity.
Right where the surgeon hasgone in, they removed all of the
cancer that they possibly can.
Sometimes they know they'veleft some behind because it's
(12:52):
involved with a major organ or ablindness or that can't be
removed.
Sometimes they know there'sgoing to be what they call
micrometastatic disease leftbehind, which is not visible to
the eye but they can have prettysure it's there.
And so in this setting wherewhat we call this an incomplete
perception of the cancer, weknow there's going to be cancer
left behind, but it's reallyabout finding the optimal window
to apply these therapies wherewe've got the best chance of
(13:13):
them being effective, because weknow if this cancer comes back,
it comes back more aggressiveand harder to treat.
And so this idea it was comingfrom orthopedics about putting
something in the wound toprevent infection we kind of
jumped on board with this andported that over to the cancer
setting with this idea ofdelivering immunotherapy
actually intraoperatively orduring that surgical procedure,
(13:34):
and that really started off forus.
What's been this massiveimmunoengineering project where
we had to come up with atreatment that we knew was going
to be safe during wound healing, because we can't be doing
anything?
That's actually, if I step backa step after a surgery, when
the wound is healing it's a veryimmune, active process, right,
there's cells coming into thatwound to start that healing
process.
We don't want to give animmunotherapy that's going to
(13:56):
affect that negatively and causewound healing to be impaired.
So it's been a real journey infinding the right therapy to
combine with the right materialto place in a wound.
That's also going to bebiodegradable, so it will break
down slowly over time and thebody will reabsorb it so the
patient doesn't have to come inand have it removed later as
it's breaking down.
It's also releasing thattherapy, that immunotherapy,
(14:17):
slowly into that local areawhere we suspect there might be
cancer cells left behind and thegoal really there is to use
that therapy to activate theimmune system so it can detect
those little bits of cancer thatare left behind.
You get a flood of immune cellscoming in which will then
destroy the cancer cells and thesurgeon and the patient can be
more surgeon that the surgeryhas actually been effective at
removing all of the cancer cells.
(14:37):
So not only we think this isgoing to be an optimal time to
apply this therapy, but we'rereally hoping that it means that
also, when we have these kidsthat are coming in with cancer,
that they're not going to haveto have this follow up
chemotherapy and radiotherapytreatments, which can be really
hard on them.
Speaker 1 (14:53):
Yeah, absolutely, did you all someone in developing
this product?
I mean, I know you did someresearch in dogs with the G.
You guys use other animalmodels and like the
developmental phase where you'retrying to figure out the best
type of polymer or best type ofway to get this in and then find
a product that's dissolvable.
I didn't interfere with woundhealing and everything that you
went on to describe that youguys needed to accomplish.
Speaker 2 (15:15):
Yeah, definitely.
So I think it's really.
We had quite a staged approachwhere we started off in the lab
in tissue culture, cell culture,testing drugs on cancer cells
to find out which drugs wethought were going to be the
most effective at attackingthese sarcoma cells.
So we did quite a lot ofscreening of drugs in tissue
culture dishes and 96 wallplates, which allows us to
screen through things reallyquickly, identify the best
(15:36):
candidates, best drugs that wethink are effective, and then we
take those and we say you knowwhich of these are applicable
for loading into biomaterial.
So we actually came up with agel.
It's a bit like a hair gel inconsistency, that's moldable,
still keeps its shape a bit andis really usable by the surgeon.
It's optimized for the surgeonto be able to be placed in the
wound and so then we took thosekind of top candidate drugs, we
(15:58):
tested them in our animal modelsof cancer.
These are mouse models of cancerand the reason that we have to
do this in an animal model isthat when we want to model an
interaction between the immunesystem and the cancer cell, we
just can't really do thateffectively in a dish in the lab
.
So we can't recapitulate thatintense complexity that we see
in the immune system and all thedifferent cell types which are
(16:20):
actually critical.
They're all critical in drivingthis immune response which
destroys the cancer cells.
We then move from that phasewhere we're treating, looking at
lots of drugs in the lab, topicking our top candidates to
then test in our, in our what wecall pre-clinical models, which
are mouse models.
We're looking at the effect ofthe animals immune system to
actually fight cancer cells andyou'd be surprised how similar a
(16:41):
mammalian immune system is ingeneral.
So, whether it's a dog, whetherit's a mouse, whether it's a
human, there's quite a lot oftranslatability across each of
those species in terms of howthe immune system works.
Speaker 1 (16:52):
Yeah, especially with mice.
I think so many people don'trealize how closely immune
system wise anyways mice andhumans really are and why
they're used.
That's what we've talked a lotabout on the show, about how
they use specifically, and a lotof immunological research out
there, and I think it'sfascinating and I think it's
still hard to play.
Our listeners find itfascinating when you think about
the vast differences betweenmice and us, obviously, but when
(17:13):
it comes to the immune system,there's so many similarities and
just the way we can engineerthem.
I think it's pretty cool.
Speaker 2 (17:18):
Yeah, it's actually quite interesting to go back to
my PhD for a second.
I came out of my PhD researchactually knowing a lot about
murine or mouse dendritic cells,because that's what I studied a
lot and there was kind of a fora long time there was a big gap
between how much we knew.
We knew so much more about themouse immune system than we did
even about the human immunesystem, and so it actually took
the human scientists and theclinicians a lot of time to
(17:40):
catch up to where we were interms of how much we understood
about the immune system, becausewe could study it so well in
these animal models.
So what we really arrived atthen was after our preclinical
animal studies was that we hadchosen our best candidate drug
and we were able to optimize thegel that we were using to
deliver it during surgery, andof course, we had to develop a
(18:00):
surgical model for this.
So we have a small animalsurgical model where we remove a
certain percentage of the tumorthat the mouse has and then
we're actually able to place thegel in that setting close up
the wound, recover the animaland then measure the
effectiveness of the gel and thedrug that we're delivering over
an extended period of time andsee how that actually prevents
(18:22):
recurrence of the cancer.
And we're able to show in anumber of different cancer types
that this drug could be reallyeffective.
Not only on its own it coulddecrease cancer recurrence on
its own but it also workedreally well with additional
immunotherapies.
Some of your listeners mighthave heard of things like immune
checkpoint blockade, which is asystemic immunotherapy which is
used in humans in clinicaltrials and now in melanoma and
(18:42):
lung cancer and can be reallyeffective.
And we found that by givingthis local therapy in the gel we
were actually able to like,sensitize some of these cancers
to respond better to these otherimmunotherapies, which was
really promising, absolutely.
And then the next step was tosay how do we make that leap
from doing a surgical model in asmall animal, in a mouse, which
(19:03):
is we're talking about 20 grams, scaling that up to a human,
that's 20, 30, 40 kilos in apediatric patient?
There had to be an intermediatestep and for us the perfect
intermediate was by doing thiscanine clinical trial.
So we actually went up to a vetclinic up the road from the
hospital and we said to them doyou see canine patients?
(19:25):
Do you get dogs that come intothe vet clinic and they have
cancer and they said, yeah, wesee these ones, we see these, we
see sarcoma all the time.
And we said, oh, that'sfantastic, we're really
interested in developing newtherapies for cancer.
Why don't we develop a clinicaltrial in collaboration with the
vet clinic?
Not only can we test oursurgically developed gel that we
have in the therapy in theanimal model that's more
(19:47):
replicative of the surgicalprocedure that you can do in a
human but we might actually alsobe able to help some beautiful
pet dogs at the same time, andif we can cure some dogs of
their sarcoma as well, that's awin-win.
Speaker 1 (19:58):
Yeah, especially, we see it quite frequently.
We see osteosarcoma at least afew times a year and I mean
typically we treatment if we cancatch early enough is to
amputate the limbs and we canwrap and see there in one of the
extremities and then if we canamputate, great, but even then a
lot of times their mediansurvival time is still 12 months
or so and if we had a betterway to treat it that'd be
(20:18):
awesome.
Speaker 2 (20:19):
Yeah, exactly, and I think it's a similar situation.
Obviously, not all owners oftheir pets are willing to sort
of make that sacrifice, and limbamputation is a pretty radical
surgery and I think that dogsactually manage quite well on
three legs when they need to.
Speaker 1 (20:34):
I mean that's really an option for humans and of
course, that'd be a very radicalsort of aggressive way to treat
it For dogs.
Yeah, most of them, I mean theydo great with three legs.
They act like you wouldn't evenknow they're operating on three
.
Sometimes, when you first walkin, it takes that second glance
to look down and go there's onlythree legs instead of four,
just because they can ambulateand get around so well.
Speaker 2 (20:54):
Yeah, for sure.
We think that the gel, though,will be that additional therapy
on top of surgery where, like Isaid, if we can hit the cancer
at that point where we hope it'sat its weakest the surgeons
removed as much of the cancer asthey can.
We just need to activate theimmune system to do its job.
We know that these immune cellsare already coming into that
wound area.
If we can just give them theright signals, activate them
(21:15):
against any cancer that's leftbehind and clean that up, that's
really going to help preventrecurrence of disease and
disease relapse, which canultimately be what ends up
causing the death of some ofthese patients.
Speaker 1 (21:26):
Absolutely so.
With the clinical trial, youall have numbers on how many
dogs you guys treated or solvedwith sarcoma and implied your
polymer immunotherapy treatmenttoo.
What's the data look like fromthat?
Speaker 2 (21:38):
Yeah, so we've just finished recruiting all our
patients.
We have one of our dogs has tocome back in and give his like
three month follow up bloodsample.
So we asked the patients thedogs to come in and give blood
before we did the surgery andthen at two weeks post-surgery,
when they would normally come inand have their post-doc checkup
, we asked the vets to takeanother sample of blood and also
to look at the wound and makesure it was healing all right
(22:00):
and that there wasn't anycomplications with that wound
healing.
Like I mentioned, we reallyneeded to make sure we're
avoiding that.
We definitely chose drugs thatwe knew weren't going to affect
wound healing in our mousemodels.
In fact, sometimes they evenmade the wound healing better.
So we're pretty confident thatit was all going to be.
You know, we had a good dataset pre-clinical models.
We're pretty sure it's going tobe fine.
We just needed to make sure inthat larger surgical setting
(22:20):
that we're seeing, you know, a30 kilo Labrador is kind of a
good model for a child in someregards in terms of the dose of
drug and the size of the surgerythat's going on and, yeah,
we've had really positiveresults.
So this was really a trial forsafety and usability of the gel
immunotherapy combo.
So the first thing the vetstold us was that the gel was
perfect for applying during thesurgeries that they were doing,
adhered nicely to the wound area, it didn't leak out, they could
(22:42):
close up the surgery and thenwhen the patients came back in,
there was no signs ofcomplications with the wounds
and the gel had degradednaturally over that period and
released all of its drugs.
So that was really good.
The other one was that ofcourse we don't say the vets,
you know, we don't want them toleave any cancer behind.
We always want them to removeall of the cancer if they can.
In every surgery we just put thegel in there as a you know, a
(23:03):
bit of an additive as well.
So we need a way to measure howeffective the gel is in
activating the immune system,and that's why we have these
blood samples, which is whatwe're following up now, and
we're using a technique calledflow cytometry which in the lab
allows us to label all thedifferent kinds of immune cells
that are in the patient's bloodsample, so white blood cells,
things like dendritic cells,macrophages and neutrophils,
which are all important in theanti-cancer response and by
(23:25):
looking at the blood samplesbefore we do the surgery and
give the immunotherapy and thenafterwards we can really look at
whether there's been a goodactivation of the immune system
that we think is going to beeffective at finding the cancer.
So it's really exciting.
We're just sort of looking atthat data now.
I can't really say too muchabout it, but we're really
hoping it's going to be reallypromising and going to show us
that we're having a good effect.
Speaker 1 (23:44):
Well, I can't wait to see some of those results and
then, hopefully, something wecan have access to at some point
down the road.
Speaker 2 (23:50):
Exactly.
There's been some really goodexamples of this translation of
drugs through veterinarypractice and into human clinical
trials as well, and that stephas been really important, I
think, in speeding up some ofthese therapies, because it does
take quite a long time it cantake seven to 10 years to get a
drug from the bench into,obviously, bench to bedside
(24:10):
where we're actually treatingpatients in a clinical trial and
so by getting that reallyimportant early data in
something like a veterinarysetting, it allows us to really
speed up that process.
It allows us to de-risk some ofthe process when we're looking
ahead and saying is this goingto be a therapy that's going to
be effective and work in a humanpatient?
So it really is important forus in the translation of these
(24:31):
therapies from an idea that wehave to the lab to the bedside.
Speaker 1 (24:35):
Yeah, absolutely.
You kind of already touchedupon this, but in your opinion,
is there any way to conduct theresearch that you all did if you
didn't have the availability ofusing animals in research?
So if you just had to realizesolely on computer models and
cell culture and stuff which youhad talked about already, and
not have actual live animals, doyou think you could still
(24:57):
develop the product or in thesame timeframe that you guys
were able to do it?
Speaker 2 (25:01):
It would be very difficult.
I mean, scientists are verysmart people.
I'm sure that we would come upwith some way to do that.
I can't think of it off the topof my head just because I
touched on this all the waythrough.
The human body is so complex.
Your immune system is socomplex.
There are so many differentcell types within your immune
system which are involved inkeeping you safe and healthy and
(25:22):
free from bugs and cancer cells.
It's really hard to model thatin a dish.
People are trying they'reworking on 3D printed organs, so
that's a really cool kind ofapplication that's come out of.
3d printing is now we can 3Dprint cells and matrices that
can kind of replace thatstructure of an organ and then
the cells can grow within thatwhich can give you the right 3D
(25:42):
sort of orientation andinteraction.
But particularly when we looktalking about immunotherapy and
looking at the response of theactive complete immune system
against a cancer cell, then itis really difficult to model
that Without being able to gothrough that process in our
preclinical animal models.
It would be a bit more of ashot in the dark when to make
that step to humans and I thinka lot more things would fail
(26:05):
because we wouldn't have that,all that data generated to
suggest that this is a prettysure bet that it's going to be
improved the outcomes of thepatients when you treat them.
So the bar is set really highwhen you want to take a therapy
into a clinical trial and starttreating human patients, and so
I think, without being able towork in some of these animal
models, it would be a lot harder.
Speaker 1 (26:24):
Yeah, really I think a lot of the applicability comes
into play.
It's not always, I mean, ofcourse efficacy is important and
critical, but really you got tohave confidence that what
you're putting in is going to beat least safe and not cause
more harm than you're trying tohelp.
Exactly, I think that's wherethe animals really come in to
help with this research.
Speaker 2 (26:43):
We couldn't do the kind of research without the
animals, and the benefit thatthey provide is really huge.
Speaker 1 (26:50):
Yeah, it's going to be tough to get people to sign
up for clinical trials anddoctors to back them if all we
have so far is some cell culturedata.
This wouldn't have thatconfidence.
But, like you said, of course,maybe at some point down the
road scientists will developsome sort of new approach that
gives us that informationwithout having to use animals.
But, like you said, I don'tknow what that is and maybe at
some point down the road we'llfind out.
(27:11):
But for now we don't have thatkind of technology.
Speaker 2 (27:14):
Yeah, and I think, like I said, scientists are a
pretty smart bunch and we'repretty inquisitive and we're
always looking for those newpotential things, because that
can be another way that we canspeed up the research as well,
or it can be really nicecomplementary technique that we
can use alongside having to useanimals.
Speaker 1 (27:29):
Yeah, Absolutely so.
We always like and you'vetalked about this a lot already
do we always like to kind ofsummarize and tell our listeners
about how your research can beapplied to the human world.
And I think if people have beenpaying attention we can already
see how it's going to beapplied to the human world.
So if you would just kind ofsummarize a little bit about how
(27:50):
your research has helpedadvance our understanding of
like sarcoma treatment optionsand then how or when do you
think we might see some of theresults of your research being
used to help out humans,particularly these children that
are suffering from sarcoma?
Speaker 2 (28:04):
Yeah, exactly, thank you.
There isn't a lot ofinformation, I guess, out there
about delivering therapiesduring surgery.
We know that this is a bit ofan underappreciated area and
it's a very important area interms of their immune response.
Our goal really in the sarcomagroup the telethon kids is to
come up with safer, moreeffective and kinder treatments
(28:24):
for these poor kids with sarcoma.
We think that that surgicalmoment when they're having the
cancer removed is that window ofopportunity for us to apply the
most effective therapies thatwe can at the moment when they
are needed.
We've really learned a lot, Ithink, about the practical
elements of this.
It's been as much animmunological project as an
engineering project.
We've collaborated with a lotof chemists and bioengineers
(28:47):
around.
Actually, what kind of gel?
How do we get the gels or atleast the drug over the period
that we need?
All the physical properties.
We've really learned a lotabout drug delivery in the
context of surgery and activeimmune area, I think.
Looking forward, we really hopethat if we can really nail this
on the head and get it working,it's going to provide an
(29:07):
entirely new way for surgeonsand oncologists to start the
living therapy in cancerpatients.
It can be applicable beyondjust sarcoma or beyond just
pediatric therapy, to a wholerange of solid cancers in adults
as well.
We've already hoping topotentially see some effect in
our canine patients, which wouldbe really awesome.
I think our job now is to takeall of this amazing data that
(29:31):
we've been able to gatherbecause we're working at animals
, because we've been able to dothe preclinical mouse models,
because we've been able to goand test in our canine
veterinary patients.
It's really our job now to takeall that data that we've been
able to generate and push aheadtowards a phase one clinical
trial in human patients Withsarcoma.
That might be in adult patientsfirst.
It might be in pediatricpatients.
(29:52):
We're certainly now lookingforward.
We're looking ahead.
We're talking to ourcollaborators who are
oncologists and surgeons at thehospitals that we're co-located
with.
We're saying to them what's thebest patient cohort that's
going to benefit from this?
Where would you like us tostart delivering this?
We're also raising money.
This isn't a trivial process.
It can be.
We're looking at even for asmall human trial a year in the
(30:14):
tens of millions of dollars weneed to get that money from
somewhere as well.
That's a constant struggle inresearch.
We're really out there we'rehitting the pavement, we're
talking to a lot of people,we're collaborating with a lot
of people and we hope to seewe'd love to see this kind of
therapy which we're pioneeringout there in the hands of
surgeons and oncologists helpingpatients with the next three to
five years.
Speaker 1 (30:34):
Awesome.
Well, if we have any extremelyphilanthropic listeners, help
them out.
One thing we like to ask all ofour listeners is just basically
, and I don't know what theculture is like.
We did talk to somebody fromNew Zealand and I know I can't
make comparisons between NewZealand and Australia I was
already corrected once on thatbut we did interview somebody
from New Zealand.
They told us a little bit aboutthe culture of animal research
(30:56):
down there and public perception.
When you go about talking topeople at a gathering, on an
airplane, at a party somewhere,about what you do for a living,
do you bring up the animalcomponent of your research?
If so, how is that perceivedand how do you explain to them
what you do?
Speaker 2 (31:10):
It is a tricky one.
You do have to be careful.
I guess sound people out alittle bit.
I focus on two things, andwe've touched on them here a
little bit as well.
Is that really the need that wehave to understand the complex
biology and actions mechanismsof the immune system that we
just can't do in any other wayat the moment?
I touch on the end point, thegoal that we're trying to
(31:31):
achieve, which is to develop newtherapies to help kids with
cancer.
To do that translation, we doneed often to work in animal
models.
I also like to tell them a bitabout the process that we go
through, because I know it'sprobably the same in New Zealand
and in the US as well.
We have quite a lot of processaround the ethics approvals that
we need to acquire.
There are ethics committeeswith a group of veterinarians,
(31:54):
scientists and lay people onthose committees that have to
approve our applications.
We work very closely with ouranimal welfare officers, who are
veterinarians, and we actuallydesigned our surgical modeling
in collaboration with our animalwelfare officer at the
institute that we work at.
We do take the best care thatwe can with these animals.
We understand that it's reallynot optimal, but they have to
have cancer and we have to tryand treat them and cure them.
(32:17):
That doesn't happen all thetime, but we do take the best
care of these animals that wepossibly can.
I like to really stress that I'man animal lover.
I grew up loving animals.
I love doing things like I usedto go and sit in my backyard
and look at all the differentbird species that came into our
backyard.
We were lucky that we had avery lush, green backyard and I
would tick off all the differentbird species that came in.
(32:39):
I've always been an animallover and I think part of that
makes working with animalsdifficult, sometimes part of it
really interesting and it's partof the reason I enjoy the
animal work.
I just try and help themunderstand and embrace the
animal work that we do.
Speaker 1 (32:54):
Yeah, that's a great way to do it.
Sometimes it's quite theconversation to have and you
have to dedicate some time toget some people to understand
and you're not going to convinceeverybody.
Just tell them how it is andlet them form their own opinions
from there.
So I appreciate you sharingthat with us.
Before we wrap up, is there anyfinal statements or anything
that we haven't covered that youthink our audience should know
(33:14):
regarding your research, animalresearch in general, sarcoma or
any other topic?
Speaker 2 (33:20):
We've covered off on all the key points.
I'd just like to say thanks,obviously to you, Jeff, for
hosting this podcast.
I think what you're doing isreally important spreading that
sort of open and honestconversation about animals in
research and it's something thatis really important as a
research community andcommunicating our research to
the broader public as well.
Thanks for leading the waythere and it's been a pleasure
(33:40):
to talk to you and all of yourlisteners.
Speaker 1 (33:42):
Yeah, it's been great and I forgot to mention in the
beginning.
Obviously Danielle's usuallyjoining us, so everyone out
there wondering where Danielleis.
She's just stuck in somemonsoon rain in Virginia and has
some work things going on, soshe couldn't join us today, but
she'll be back.
It just couldn't make it happentoday and I didn't want to try
to reschedule today's episodejust because of the time
difference and everything goingon and it would have been last
(34:05):
minute.
So thank you for beingaccommodating and staying up.
I guess it's not too late overthere.
Speaker 2 (34:10):
No, it's not too bad.
Speaker 1 (34:11):
Thanks for accommodating our time
difference and making it happenand sharing with our listeners
everything about your researchand telling us about Sarcoma,
and it would be great to hear.
Make sure you follow up with us.
When you guys do get some datafrom your clinical trials and
we're able to share some of thatdata with our listeners, or any
publications you guys put out,send them over to us.
(34:32):
We'll share them.
We'll go ahead and share.
If you have links to yourresearch webpage or your
institute, definitely send thatto us.
We'll share it with everyonethat's listening to this episode
and everyone that's listeningto you.
You know where to find thoselinks on our social media pages
or they'll also be embeddedwithin the show notes of today's
episode.
All right, so thank you so much, ben, for joining us today.
(34:52):
It's been a pleasure talkingwith you.
Speaker 2 (34:53):
It's been a pleasure, jeff, really lovely to talk to
you as well.
Speaker 1 (34:57):
Absolutely Everyone.
Please take a minute to rate.
Review our show again.
Email us LibratChat at gmailcom.
If you have questions, topics,you want us to cover anything of
the sorts, we appreciate it andwe will catch everyone next
time.
See everyone, bye-bye.
This podcast is supported by Americans for
Medical Progress and was foundedand created through the Michael
D Hare Fellowship, awardedannually to support projects
that inform and educate thepublic about the critical role
of animal research in furtheringmedical progress.
The Fellowship honors the lateDr Michael Hare, a renowned
board-certified laboratoryanimal veterinarian who
dedicated his career toscientific and medical
(00:25):
advancements and who was deeplycommitted to animal welfare and
advocacy.
We've got Dr Wiley with ustoday.
He's going to talk to us aboutsome sarcoma research some
(00:45):
really cool stuff they're doingthere.
As part of our promotion ofJuly is in the US, new A's
National Sarcoma Awareness Month.
He's going to give us somereally good information about
what sarcoma is, some of theresearch they're doing there.
Now let him tell you all aboutthat.
But before we get started, I dojust want to tell everybody out
there to please go on socialmedia rate review our show, make
(01:09):
comments on our posts, followus on Instagram.
If you're listening to this, onSpotify, apple iTunes the great
thing is this is not live.
You have the opportunity topress pause.
Rate review the podcast.
It really helps our exposure.
More people can find us, morepeople can hear us, more people
can find out about what Librachat's all about.
So thank you for everyone fordoing that.
(01:29):
We've noticed more and morefollowers lately, and I think
it's all because of ourdedicated listeners out there.
So thank you for that.
And with that, let's go aheadand get into today's episode.
So, dr Wiley, if you will justtell us a little bit about your
background, what made you sointerested in research and
science, and just give us alittle description of the
journey to get where you're atin your career today, Thanks,
(01:50):
jeff, and of course, thanks forhaving me on the podcast.
Speaker 2 (01:52):
It's fantastic.
I think the work you guys aredoing you know, telling everyone
about the awesome researchthat's going on and all the
animal work that we're doing isreally important.
So I think most people'sjourney into research and
certainly my journey starts withcuriosity.
It's probably the key aspect ofyou know what drives people's
desire for research, and it'sreally that wanting to
(02:12):
understand why and how thingswork.
And for me that really startedoff early on in my life in
thinking and looking at thenatural world.
So I was really interested inanimals documentaries and I
actually wanted to be aveterinarian at a very early
sort of young age.
Didn't quite get the grades todo that straight out of school,
so I chose actually to go touniversity and study biomedical
science and from there that'sreally where my research
(02:34):
interest sort of was firstpiqued and the research journey
began.
I think the real likerevelation for me came in
finding a topic that I wasreally interested in and that
was, you know, a third yearuniversity.
You know that I taught inimmunology and learning all
about the immune system, howeverything worked, all the
things that were going on insidemy body.
That was really fascinating.
And at the same time I did aresearch project over the summer
(02:57):
break at uni and I worked in alab that was focused on the
genetics of wheat fungus, whichI thought was really pretty
boring, but I knew I likedworking in the lab.
That showed me I liked workingin the lab.
So from there I had this ideathat's where I wanted to end up
doing research.
It took looking around for youknow, a few different jobs to
find a place where I couldreally apply that for immunology
(03:17):
in an area that I felt couldhave a real positive impact, and
that ended up being in cancerresearch.
And so, you know, I had acouple of research assistant
jobs where I learned a lot ofskills and that really led me on
to, you know, my PhD, which wasat the telecom kids institute,
working in the cancer center,and there I was looking at
specific immune cells calleddendritic cells and they have a
(03:38):
role in your body which is todetect cancer and other things
like viruses and bacteria and toactivate your immune system to
destroy those pathogens.
And really when I was startingmy PhD, we were just sort of
learning that your immune systemcan be activated to destroy
those cancer cells, and thefirst research was coming out of
labs in America showing thatthere was real potential in
using this as a therapy forcancer patients.
(04:00):
So my career path didn'tnecessarily always take that
straight line, like you mightthink.
There have been times where Iwasn't certain what my research
future was going to hold.
After my PhD I took a bit of aleft turn.
I took a job at a local drugdiscovery company and I worked
there for a couple of yearsdeveloping a range of different
therapies across different areas, and that gave me a really good
look at, you know, thecommercial side of research,
(04:21):
which is really focused onpushing a drug candidate to the
clinic, and that was kind ofrefreshing because it wasn't
something I'd done during my PhD.
My PhD research had been verysort of fundamental, but some
people call basic research aboutyou know how the cells of your
immune system function andinteract with cancer, so that
was really interesting.
However, I still felt that pullfrom you know academic research
, like I still had somethingleft to do, something unfinished
(04:42):
there, and so when the chancecame to sort of move back to
Telethon kids with a new groupthat was starting up there, I
jumped right in and I haven'tlooked back.
And that group is the sarcomagroup.
They're looking at developingnew, safer and more effective
ways to treat pediatric sarcomaand help kids who have this
terrible cancer.
Speaker 1 (04:59):
Yeah, that's awesome.
It seems like it's a cancer thatdoes affect, unfortunately, a
lot of children.
I can definitely relate to alittle bit of your journey about
not having the greats to getinto vet school.
I didn't have a right out ofundergrad and out of getting my
master's degree and ended up aseveryone that listens to this
show knows, because I say itover and over is I had a 10 year
gap between graduate, myundergrad, until applying to vet
(05:21):
school and really I didn't havethese huge intentions of going
to vet school right away and itwas something that my career
within the field of biomedicalresearch led me to wanting to go
to vet school.
But had I tried to apply to vetschool right out of undergrad?
There's no way, and so I wasable to kind of build up my
resume by showing all thisexperience with animals and in
that way.
So I'm thankful for my journeyand no one really has that
(05:42):
straight path to get to wherethey are, and I think that's
what makes everyone's story sointeresting and it's always cool
to hear everyone's story andbackground, so appreciate that.
Speaker 2 (05:51):
It's funny I'll touch on it a little bit later but I
actually almost converted overto vet school during my
undergrad degree and one of thereasons that I thought I'm not
really sure about vet school isbecause I wasn't sure how I
would handle having to dosurgery on animals.
And I guess as I'll touch on abit later you know, in my
current project that's actuallyone of the things I've gone back
to and a skill that I'velearned.
So it's funny how these thingscome around.
Speaker 1 (06:10):
Yeah, absolutely so, all right.
Well, since July, let's say, Iknow it was actually August 4th,
so for everyone listening, wedidn't get this out in July, but
July that was our intention.
Scheduling can be difficultwhen we're halfway across the
world.
July is our coma healthawareness month.
So let's first you've alreadytalked about it a little bit
what exactly is sarcoma, youknow?
Just give us some background onthat, as much information as
(06:33):
you can about you know how manypeople might be living with it.
Is it aggressive, nonaggressive, that sort of thing.
Speaker 2 (06:39):
So sarcomas are really a group of cancers.
We kind of linked them all inunder this one name of sarcoma.
But they're generally solidcancers that form in the
connective tissues of your body.
So these can be things like inthe muscle, in the fat around
nerves and just generally in theconnective tissue that holds
your body together.
Sarcomas are actuallyreasonably rare in adults.
They're actually much morecommon in kids.
(07:00):
They're the third most commoncancer, behind blood cancer and
cancer in kids, although overall, thankfully, childhood cancers
are actually very rare incomparison to cancer in adults.
So I think in the US the totalis about 15,000 people a year
diagnosed with sarcoma and abouta thousand of those will be
kids.
At the Telethon Kids Institute,where I work, we're really
focused.
We're a kids research institute, we're focused on pediatric
(07:23):
oncology and pediatric cancersand for kids sarcoma is a very
serious disease.
One in three kids still diefrom sarcoma, despite our best
efforts and the best currenttherapies that we have.
And indeed sarcomas can be quitelocally aggressive and because
they're a solo cancer, the mainsort of first intervention that
an oncologist will normallyprescribe is a surgery to remove
(07:44):
a lump.
So anecdotally, we hear thesestories of kids.
Actually, you know they'll havea bit of a lump somewhere on
their body.
It's actually quite interesting.
Often they'll have like asporting mishap or an injury, or
they'll fall over and bumptheir leg and they'll say, oh,
that really hurts.
And they'll tell their parentsthat they've got this bump.
That hurts and it just doesn'tseem to get better over time,
and then so that results in atrip to the doctor and, you know
(08:05):
, a biopsy or something of thislump, and then often it turns
out to be a sarcoma.
We call this a solo cancer.
It's a lump.
It can be removed surgicallyand that's generally the first
treatment that is prescribed.
The oncologist or the surgeonwill go in.
They'll do a surgery to try andremove all of the sarcoma, if
they can.
Often because sarcoma isinvolved in connective tissue,
so around the, around the organsinvolved with nerves, it's
(08:27):
often not possible to remove allof that cancer in one go, and
so this is one of the mainproblems with sarcoma.
They're quite locally invasiveand aggressive, and because
surgeries aren't alwayseffective, it means that the
patients have to have follow up,chemo and radiotherapy.
It's also quite interesting.
We do interact with both adultsurgeons and then the pediatric
surgeons at the hospital thatwe're located in in Perth and
(08:50):
the kind of surgeries thatthey'll do are also quite
different.
So the kind of surgery that youmight apply, the surgical
approach that you might apply inan adult is very different than
in a pediatric patient as well,where they there's a real
preference not to do, you know,major surgery, not to limb
removal surgery and things likethat, because obviously that's
going to massively affect apediatric patient or a child's
(09:10):
ongoing wellbeing and state oflife throughout the rest of
their life, even if they arecured of their sarcoma.
It's really on us in theresearch side to start coming up
with better therapies that canhelp these kids with sarcoma.
That's what our lab is allabout.
We say it telephone kids and inthe cancer center we're all
about developing safer andkinder therapies for kids.
Speaker 1 (09:28):
So in like in dogs for example, osteosarcoma is a
really big one.
Is that pretty common inchildren also?
Is it more soft tissue?
Speaker 2 (09:36):
The three big ones in kids are osteosarcomas, and
then there are a couple of softtissue sarcomas which we're sort
of interested in particularly,and then another group which are
called rabdomyosarcomas, andthese are the ones that form in
the muscles Interesting in kids.
They all affect slightlydifferent age groups as well, so
some will affect very youngkids, some will really affect
the kids as they're becomingadolescents and young adults.
(09:56):
So turning into teenagers andyoung adults, there's a
crossover there in theclinicians and how they're
treated when they're sort oftransitioning through that phase
from being an older kid to ayoung adult, to a full adult,
and that can affect the kind ofcancer treatment that they
receive.
Speaker 1 (10:10):
Yeah, absolutely, and I guess the success rate on
their treatment is going todepend on many variables, such
as how early they catch it, howinvasive it already is, whether
or not it's already spread andthat sort of thing.
Speaker 2 (10:21):
Yeah, of course.
Speaker 1 (10:23):
So yeah, since you already talked about some of
those treatment options outthere, just tell us a little bit
specifically about your team'sresearch and that novel type of
I believe you guys are doingsome immunotherapy delivery and
a unique system.
So how'd you guys come up withthat idea and then talk to us a
little bit about some of thoseresults so far?
Speaker 2 (10:42):
Yeah, sure, I mean I'll touch on the current kind
of state of play, I guess,because it's important to know
that there's a lot of researchthat's gone on over the last 30
to 50 years for cancer patientsaround chemotherapy and
radiotherapy.
The number of people survivingthese cancers is, you know,
we've done really the best thatwe can, but for sarcoma in
particular and in pediatricpatients, the state of play
(11:02):
hasn't really changed for maybe10 or 15 years.
They haven't been those steadyimprovements anymore with those
kind of traditional therapiesand that's why we're really
focused on immunotherapy.
The other reason that I thinkthe whole of the Telephone Kids
Cancer Center, where I work, isreally focused on immunotherapy
is we know that chemotherapy andradiotherapy they do require
high doses of treatment.
There can be toxicitiesassociated with these treatments
(11:24):
and in kids particularly, thesecan be long-term developmental
side effects that can really goon and affect the kids after for
a long period of time, evenafter they're cured of their
cancer.
So immunotherapy for usrepresents a way to, you know,
potentially increase the ratesof people that were curing of
cancer, while also reducingthose side effects that we see
from chemotherapy andradiotherapy.
(11:45):
And that's really, I guess,where this whole project was
born from Anecdotally my PI,who's the head of the lab that I
work in.
He began his life as anoncologist before moving
completely to the research field, so he was so in love with
research he sort of saw the needfor research being so strong
that he completely jumped overto the research world and now is
100% focused on cancer research.
(12:07):
He was actually working withorthopedic surgeons at a certain
time while working with sarcomapatients in his oncology clinic
, and that interaction sort ofled him to this idea.
In orthopedics, often whenthey're doing something like a
hip replacement, they'll placesomething in that wound site
which is either coated orembedded with antibiotics to try
and prevent infection aftersurgery, and so that sort of
(12:29):
sparked our idea is to well, ifwe can use a material to deliver
antibiotics during surgery, whynot a material that we can
actually deliver immunotherapyduring surgery as well?
And this really sort of becameup with this concept of surgery
being this window of opportunity.
Right where the surgeon hasgone in, they removed all of the
cancer that they possibly can.
Sometimes they know they'veleft some behind because it's
(12:52):
involved with a major organ or ablindness or that can't be
removed.
Sometimes they know there'sgoing to be what they call
micrometastatic disease leftbehind, which is not visible to
the eye but they can have prettysure it's there.
And so in this setting wherewhat we call this an incomplete
perception of the cancer, weknow there's going to be cancer
left behind, but it's reallyabout finding the optimal window
to apply these therapies wherewe've got the best chance of
(13:13):
them being effective, because weknow if this cancer comes back,
it comes back more aggressiveand harder to treat.
And so this idea it was comingfrom orthopedics about putting
something in the wound toprevent infection we kind of
jumped on board with this andported that over to the cancer
setting with this idea ofdelivering immunotherapy
actually intraoperatively orduring that surgical procedure,
(13:34):
and that really started off forus.
What's been this massiveimmunoengineering project where
we had to come up with atreatment that we knew was going
to be safe during wound healing, because we can't be doing
anything?
That's actually, if I step backa step after a surgery, when
the wound is healing it's a veryimmune, active process, right,
there's cells coming into thatwound to start that healing
process.
We don't want to give animmunotherapy that's going to
(13:56):
affect that negatively and causewound healing to be impaired.
So it's been a real journey infinding the right therapy to
combine with the right materialto place in a wound.
That's also going to bebiodegradable, so it will break
down slowly over time and thebody will reabsorb it so the
patient doesn't have to come inand have it removed later as
it's breaking down.
It's also releasing thattherapy, that immunotherapy,
(14:17):
slowly into that local areawhere we suspect there might be
cancer cells left behind and thegoal really there is to use
that therapy to activate theimmune system so it can detect
those little bits of cancer thatare left behind.
You get a flood of immune cellscoming in which will then
destroy the cancer cells and thesurgeon and the patient can be
more surgeon that the surgeryhas actually been effective at
removing all of the cancer cells.
(14:37):
So not only we think this isgoing to be an optimal time to
apply this therapy, but we'rereally hoping that it means that
also, when we have these kidsthat are coming in with cancer,
that they're not going to haveto have this follow up
chemotherapy and radiotherapytreatments, which can be really
hard on them.
Speaker 1 (14:53):
Yeah, absolutely, did you all someone in developing
this product?
I mean, I know you did someresearch in dogs with the G.
You guys use other animalmodels and like the
developmental phase where you'retrying to figure out the best
type of polymer or best type ofway to get this in and then find
a product that's dissolvable.
I didn't interfere with woundhealing and everything that you
went on to describe that youguys needed to accomplish.
Speaker 2 (15:15):
Yeah, definitely.
So I think it's really.
We had quite a staged approachwhere we started off in the lab
in tissue culture, cell culture,testing drugs on cancer cells
to find out which drugs wethought were going to be the
most effective at attackingthese sarcoma cells.
So we did quite a lot ofscreening of drugs in tissue
culture dishes and 96 wallplates, which allows us to
screen through things reallyquickly, identify the best
(15:36):
candidates, best drugs that wethink are effective, and then we
take those and we say you knowwhich of these are applicable
for loading into biomaterial.
So we actually came up with agel.
It's a bit like a hair gel inconsistency, that's moldable,
still keeps its shape a bit andis really usable by the surgeon.
It's optimized for the surgeonto be able to be placed in the
wound and so then we took thosekind of top candidate drugs, we
(15:58):
tested them in our animal modelsof cancer.
These are mouse models of cancerand the reason that we have to
do this in an animal model isthat when we want to model an
interaction between the immunesystem and the cancer cell, we
just can't really do thateffectively in a dish in the lab
.
So we can't recapitulate thatintense complexity that we see
in the immune system and all thedifferent cell types which are
(16:20):
actually critical.
They're all critical in drivingthis immune response which
destroys the cancer cells.
We then move from that phasewhere we're treating, looking at
lots of drugs in the lab, topicking our top candidates to
then test in our, in our what wecall pre-clinical models, which
are mouse models.
We're looking at the effect ofthe animals immune system to
actually fight cancer cells andyou'd be surprised how similar a
(16:41):
mammalian immune system is ingeneral.
So, whether it's a dog, whetherit's a mouse, whether it's a
human, there's quite a lot oftranslatability across each of
those species in terms of howthe immune system works.
Speaker 1 (16:52):
Yeah, especially with mice.
I think so many people don'trealize how closely immune
system wise anyways mice andhumans really are and why
they're used.
That's what we've talked a lotabout on the show, about how
they use specifically, and a lotof immunological research out
there, and I think it'sfascinating and I think it's
still hard to play.
Our listeners find itfascinating when you think about
the vast differences betweenmice and us, obviously, but when
(17:13):
it comes to the immune system,there's so many similarities and
just the way we can engineerthem.
I think it's pretty cool.
Speaker 2 (17:18):
Yeah, it's actually quite interesting to go back to
my PhD for a second.
I came out of my PhD researchactually knowing a lot about
murine or mouse dendritic cells,because that's what I studied a
lot and there was kind of a fora long time there was a big gap
between how much we knew.
We knew so much more about themouse immune system than we did
even about the human immunesystem, and so it actually took
the human scientists and theclinicians a lot of time to
(17:40):
catch up to where we were interms of how much we understood
about the immune system, becausewe could study it so well in
these animal models.
So what we really arrived atthen was after our preclinical
animal studies was that we hadchosen our best candidate drug
and we were able to optimize thegel that we were using to
deliver it during surgery, andof course, we had to develop a
(18:00):
surgical model for this.
So we have a small animalsurgical model where we remove a
certain percentage of the tumorthat the mouse has and then
we're actually able to place thegel in that setting close up
the wound, recover the animaland then measure the
effectiveness of the gel and thedrug that we're delivering over
an extended period of time andsee how that actually prevents
(18:22):
recurrence of the cancer.
And we're able to show in anumber of different cancer types
that this drug could be reallyeffective.
Not only on its own it coulddecrease cancer recurrence on
its own but it also workedreally well with additional
immunotherapies.
Some of your listeners mighthave heard of things like immune
checkpoint blockade, which is asystemic immunotherapy which is
used in humans in clinicaltrials and now in melanoma and
(18:42):
lung cancer and can be reallyeffective.
And we found that by givingthis local therapy in the gel we
were actually able to like,sensitize some of these cancers
to respond better to these otherimmunotherapies, which was
really promising, absolutely.
And then the next step was tosay how do we make that leap
from doing a surgical model in asmall animal, in a mouse, which
(19:03):
is we're talking about 20 grams, scaling that up to a human,
that's 20, 30, 40 kilos in apediatric patient?
There had to be an intermediatestep and for us the perfect
intermediate was by doing thiscanine clinical trial.
So we actually went up to a vetclinic up the road from the
hospital and we said to them doyou see canine patients?
(19:25):
Do you get dogs that come intothe vet clinic and they have
cancer and they said, yeah, wesee these ones, we see these, we
see sarcoma all the time.
And we said, oh, that'sfantastic, we're really
interested in developing newtherapies for cancer.
Why don't we develop a clinicaltrial in collaboration with the
vet clinic?
Not only can we test oursurgically developed gel that we
have in the therapy in theanimal model that's more
(19:47):
replicative of the surgicalprocedure that you can do in a
human but we might actually alsobe able to help some beautiful
pet dogs at the same time, andif we can cure some dogs of
their sarcoma as well, that's awin-win.
Speaker 1 (19:58):
Yeah, especially, we see it quite frequently.
We see osteosarcoma at least afew times a year and I mean
typically we treatment if we cancatch early enough is to
amputate the limbs and we canwrap and see there in one of the
extremities and then if we canamputate, great, but even then a
lot of times their mediansurvival time is still 12 months
or so and if we had a betterway to treat it that'd be
(20:18):
awesome.
Speaker 2 (20:19):
Yeah, exactly, and I think it's a similar situation.
Obviously, not all owners oftheir pets are willing to sort
of make that sacrifice, and limbamputation is a pretty radical
surgery and I think that dogsactually manage quite well on
three legs when they need to.
Speaker 1 (20:34):
I mean that's really an option for humans and of
course, that'd be a very radicalsort of aggressive way to treat
it For dogs.
Yeah, most of them, I mean theydo great with three legs.
They act like you wouldn't evenknow they're operating on three
.
Sometimes, when you first walkin, it takes that second glance
to look down and go there's onlythree legs instead of four,
just because they can ambulateand get around so well.
Speaker 2 (20:54):
Yeah, for sure.
We think that the gel, though,will be that additional therapy
on top of surgery where, like Isaid, if we can hit the cancer
at that point where we hope it'sat its weakest the surgeons
removed as much of the cancer asthey can.
We just need to activate theimmune system to do its job.
We know that these immune cellsare already coming into that
wound area.
If we can just give them theright signals, activate them
(21:15):
against any cancer that's leftbehind and clean that up, that's
really going to help preventrecurrence of disease and
disease relapse, which canultimately be what ends up
causing the death of some ofthese patients.
Speaker 1 (21:26):
Absolutely so.
With the clinical trial, youall have numbers on how many
dogs you guys treated or solvedwith sarcoma and implied your
polymer immunotherapy treatmenttoo.
What's the data look like fromthat?
Speaker 2 (21:38):
Yeah, so we've just finished recruiting all our
patients.
We have one of our dogs has tocome back in and give his like
three month follow up bloodsample.
So we asked the patients thedogs to come in and give blood
before we did the surgery andthen at two weeks post-surgery,
when they would normally come inand have their post-doc checkup
, we asked the vets to takeanother sample of blood and also
to look at the wound and makesure it was healing all right
(22:00):
and that there wasn't anycomplications with that wound
healing.
Like I mentioned, we reallyneeded to make sure we're
avoiding that.
We definitely chose drugs thatwe knew weren't going to affect
wound healing in our mousemodels.
In fact, sometimes they evenmade the wound healing better.
So we're pretty confident thatit was all going to be.
You know, we had a good dataset pre-clinical models.
We're pretty sure it's going tobe fine.
We just needed to make sure inthat larger surgical setting
(22:20):
that we're seeing, you know, a30 kilo Labrador is kind of a
good model for a child in someregards in terms of the dose of
drug and the size of the surgerythat's going on and, yeah,
we've had really positiveresults.
So this was really a trial forsafety and usability of the gel
immunotherapy combo.
So the first thing the vetstold us was that the gel was
perfect for applying during thesurgeries that they were doing,
adhered nicely to the wound area, it didn't leak out, they could
(22:42):
close up the surgery and thenwhen the patients came back in,
there was no signs ofcomplications with the wounds
and the gel had degradednaturally over that period and
released all of its drugs.
So that was really good.
The other one was that ofcourse we don't say the vets,
you know, we don't want them toleave any cancer behind.
We always want them to removeall of the cancer if they can.
In every surgery we just put thegel in there as a you know, a
(23:03):
bit of an additive as well.
So we need a way to measure howeffective the gel is in
activating the immune system,and that's why we have these
blood samples, which is whatwe're following up now, and
we're using a technique calledflow cytometry which in the lab
allows us to label all thedifferent kinds of immune cells
that are in the patient's bloodsample, so white blood cells,
things like dendritic cells,macrophages and neutrophils,
which are all important in theanti-cancer response and by
(23:25):
looking at the blood samplesbefore we do the surgery and
give the immunotherapy and thenafterwards we can really look at
whether there's been a goodactivation of the immune system
that we think is going to beeffective at finding the cancer.
So it's really exciting.
We're just sort of looking atthat data now.
I can't really say too muchabout it, but we're really
hoping it's going to be reallypromising and going to show us
that we're having a good effect.
Speaker 1 (23:44):
Well, I can't wait to see some of those results and
then, hopefully, something wecan have access to at some point
down the road.
Speaker 2 (23:50):
Exactly.
There's been some really goodexamples of this translation of
drugs through veterinarypractice and into human clinical
trials as well, and that stephas been really important, I
think, in speeding up some ofthese therapies, because it does
take quite a long time it cantake seven to 10 years to get a
drug from the bench into,obviously, bench to bedside
(24:10):
where we're actually treatingpatients in a clinical trial and
so by getting that reallyimportant early data in
something like a veterinarysetting, it allows us to really
speed up that process.
It allows us to de-risk some ofthe process when we're looking
ahead and saying is this goingto be a therapy that's going to
be effective and work in a humanpatient?
So it really is important forus in the translation of these
(24:31):
therapies from an idea that wehave to the lab to the bedside.
Speaker 1 (24:35):
Yeah, absolutely.
You kind of already touchedupon this, but in your opinion,
is there any way to conduct theresearch that you all did if you
didn't have the availability ofusing animals in research?
So if you just had to realizesolely on computer models and
cell culture and stuff which youhad talked about already, and
not have actual live animals, doyou think you could still
(24:57):
develop the product or in thesame timeframe that you guys
were able to do it?
Speaker 2 (25:01):
It would be very difficult.
I mean, scientists are verysmart people.
I'm sure that we would come upwith some way to do that.
I can't think of it off the topof my head just because I
touched on this all the waythrough.
The human body is so complex.
Your immune system is socomplex.
There are so many differentcell types within your immune
system which are involved inkeeping you safe and healthy and
(25:22):
free from bugs and cancer cells.
It's really hard to model thatin a dish.
People are trying they'reworking on 3D printed organs, so
that's a really cool kind ofapplication that's come out of.
3d printing is now we can 3Dprint cells and matrices that
can kind of replace thatstructure of an organ and then
the cells can grow within thatwhich can give you the right 3D
(25:42):
sort of orientation andinteraction.
But particularly when we looktalking about immunotherapy and
looking at the response of theactive complete immune system
against a cancer cell, then itis really difficult to model
that Without being able to gothrough that process in our
preclinical animal models.
It would be a bit more of ashot in the dark when to make
that step to humans and I thinka lot more things would fail
(26:05):
because we wouldn't have that,all that data generated to
suggest that this is a prettysure bet that it's going to be
improved the outcomes of thepatients when you treat them.
So the bar is set really highwhen you want to take a therapy
into a clinical trial and starttreating human patients, and so
I think, without being able towork in some of these animal
models, it would be a lot harder.
Speaker 1 (26:24):
Yeah, really I think a lot of the applicability comes
into play.
It's not always, I mean, ofcourse efficacy is important and
critical, but really you got tohave confidence that what
you're putting in is going to beat least safe and not cause
more harm than you're trying tohelp.
Exactly, I think that's wherethe animals really come in to
help with this research.
Speaker 2 (26:43):
We couldn't do the kind of research without the
animals, and the benefit thatthey provide is really huge.
Speaker 1 (26:50):
Yeah, it's going to be tough to get people to sign
up for clinical trials anddoctors to back them if all we
have so far is some cell culturedata.
This wouldn't have thatconfidence.
But, like you said, of course,maybe at some point down the
road scientists will developsome sort of new approach that
gives us that informationwithout having to use animals.
But, like you said, I don'tknow what that is and maybe at
some point down the road we'llfind out.
(27:11):
But for now we don't have thatkind of technology.
Speaker 2 (27:14):
Yeah, and I think, like I said, scientists are a
pretty smart bunch and we'repretty inquisitive and we're
always looking for those newpotential things, because that
can be another way that we canspeed up the research as well,
or it can be really nicecomplementary technique that we
can use alongside having to useanimals.
Speaker 1 (27:29):
Yeah, Absolutely so.
We always like and you'vetalked about this a lot already
do we always like to kind ofsummarize and tell our listeners
about how your research can beapplied to the human world.
And I think if people have beenpaying attention we can already
see how it's going to beapplied to the human world.
So if you would just kind ofsummarize a little bit about how
(27:50):
your research has helpedadvance our understanding of
like sarcoma treatment optionsand then how or when do you
think we might see some of theresults of your research being
used to help out humans,particularly these children that
are suffering from sarcoma?
Speaker 2 (28:04):
Yeah, exactly, thank you.
There isn't a lot ofinformation, I guess, out there
about delivering therapiesduring surgery.
We know that this is a bit ofan underappreciated area and
it's a very important area interms of their immune response.
Our goal really in the sarcomagroup the telethon kids is to
come up with safer, moreeffective and kinder treatments
(28:24):
for these poor kids with sarcoma.
We think that that surgicalmoment when they're having the
cancer removed is that window ofopportunity for us to apply the
most effective therapies thatwe can at the moment when they
are needed.
We've really learned a lot, Ithink, about the practical
elements of this.
It's been as much animmunological project as an
engineering project.
We've collaborated with a lotof chemists and bioengineers
(28:47):
around.
Actually, what kind of gel?
How do we get the gels or atleast the drug over the period
that we need?
All the physical properties.
We've really learned a lotabout drug delivery in the
context of surgery and activeimmune area, I think.
Looking forward, we really hopethat if we can really nail this
on the head and get it working,it's going to provide an
(29:07):
entirely new way for surgeonsand oncologists to start the
living therapy in cancerpatients.
It can be applicable beyondjust sarcoma or beyond just
pediatric therapy, to a wholerange of solid cancers in adults
as well.
We've already hoping topotentially see some effect in
our canine patients, which wouldbe really awesome.
I think our job now is to takeall of this amazing data that
(29:31):
we've been able to gatherbecause we're working at animals
, because we've been able to dothe preclinical mouse models,
because we've been able to goand test in our canine
veterinary patients.
It's really our job now to takeall that data that we've been
able to generate and push aheadtowards a phase one clinical
trial in human patients Withsarcoma.
That might be in adult patientsfirst.
It might be in pediatricpatients.
(29:52):
We're certainly now lookingforward.
We're looking ahead.
We're talking to ourcollaborators who are
oncologists and surgeons at thehospitals that we're co-located
with.
We're saying to them what's thebest patient cohort that's
going to benefit from this?
Where would you like us tostart delivering this?
We're also raising money.
This isn't a trivial process.
It can be.
We're looking at even for asmall human trial a year in the
(30:14):
tens of millions of dollars weneed to get that money from
somewhere as well.
That's a constant struggle inresearch.
We're really out there we'rehitting the pavement, we're
talking to a lot of people,we're collaborating with a lot
of people and we hope to seewe'd love to see this kind of
therapy which we're pioneeringout there in the hands of
surgeons and oncologists helpingpatients with the next three to
five years.
Speaker 1 (30:34):
Awesome.
Well, if we have any extremelyphilanthropic listeners, help
them out.
One thing we like to ask all ofour listeners is just basically
, and I don't know what theculture is like.
We did talk to somebody fromNew Zealand and I know I can't
make comparisons between NewZealand and Australia I was
already corrected once on thatbut we did interview somebody
from New Zealand.
They told us a little bit aboutthe culture of animal research
(30:56):
down there and public perception.
When you go about talking topeople at a gathering, on an
airplane, at a party somewhere,about what you do for a living,
do you bring up the animalcomponent of your research?
If so, how is that perceivedand how do you explain to them
what you do?
Speaker 2 (31:10):
It is a tricky one.
You do have to be careful.
I guess sound people out alittle bit.
I focus on two things, andwe've touched on them here a
little bit as well.
Is that really the need that wehave to understand the complex
biology and actions mechanismsof the immune system that we
just can't do in any other wayat the moment?
I touch on the end point, thegoal that we're trying to
(31:31):
achieve, which is to develop newtherapies to help kids with
cancer.
To do that translation, we doneed often to work in animal
models.
I also like to tell them a bitabout the process that we go
through, because I know it'sprobably the same in New Zealand
and in the US as well.
We have quite a lot of processaround the ethics approvals that
we need to acquire.
There are ethics committeeswith a group of veterinarians,
(31:54):
scientists and lay people onthose committees that have to
approve our applications.
We work very closely with ouranimal welfare officers, who are
veterinarians, and we actuallydesigned our surgical modeling
in collaboration with our animalwelfare officer at the
institute that we work at.
We do take the best care thatwe can with these animals.
We understand that it's reallynot optimal, but they have to
have cancer and we have to tryand treat them and cure them.
(32:17):
That doesn't happen all thetime, but we do take the best
care of these animals that wepossibly can.
I like to really stress that I'man animal lover.
I grew up loving animals.
I love doing things like I usedto go and sit in my backyard
and look at all the differentbird species that came into our
backyard.
We were lucky that we had avery lush, green backyard and I
would tick off all the differentbird species that came in.
(32:39):
I've always been an animallover and I think part of that
makes working with animalsdifficult, sometimes part of it
really interesting and it's partof the reason I enjoy the
animal work.
I just try and help themunderstand and embrace the
animal work that we do.
Speaker 1 (32:54):
Yeah, that's a great way to do it.
Sometimes it's quite theconversation to have and you
have to dedicate some time toget some people to understand
and you're not going to convinceeverybody.
Just tell them how it is andlet them form their own opinions
from there.
So I appreciate you sharingthat with us.
Before we wrap up, is there anyfinal statements or anything
that we haven't covered that youthink our audience should know
(33:14):
regarding your research, animalresearch in general, sarcoma or
any other topic?
Speaker 2 (33:20):
We've covered off on all the key points.
I'd just like to say thanks,obviously to you, Jeff, for
hosting this podcast.
I think what you're doing isreally important spreading that
sort of open and honestconversation about animals in
research and it's something thatis really important as a
research community andcommunicating our research to
the broader public as well.
Thanks for leading the waythere and it's been a pleasure
(33:40):
to talk to you and all of yourlisteners.
Speaker 1 (33:42):
Yeah, it's been great and I forgot to mention in the
beginning.
Obviously Danielle's usuallyjoining us, so everyone out
there wondering where Danielleis.
She's just stuck in somemonsoon rain in Virginia and has
some work things going on, soshe couldn't join us today, but
she'll be back.
It just couldn't make it happentoday and I didn't want to try
to reschedule today's episodejust because of the time
difference and everything goingon and it would have been last
(34:05):
minute.
So thank you for beingaccommodating and staying up.
I guess it's not too late overthere.
Speaker 2 (34:10):
No, it's not too bad.
Speaker 1 (34:11):
Thanks for accommodating our time
difference and making it happenand sharing with our listeners
everything about your researchand telling us about Sarcoma,
and it would be great to hear.
Make sure you follow up with us.
When you guys do get some datafrom your clinical trials and
we're able to share some of thatdata with our listeners, or any
publications you guys put out,send them over to us.
(34:32):
We'll share them.
We'll go ahead and share.
If you have links to yourresearch webpage or your
institute, definitely send thatto us.
We'll share it with everyonethat's listening to this episode
and everyone that's listeningto you.
You know where to find thoselinks on our social media pages
or they'll also be embeddedwithin the show notes of today's
episode.
All right, so thank you so much, ben, for joining us today.
(34:52):
It's been a pleasure talkingwith you.
Speaker 2 (34:53):
It's been a pleasure, jeff, really lovely to talk to
you as well.
Speaker 1 (34:57):
Absolutely Everyone.
Please take a minute to rate.
Review our show again.
Email us LibratChat at gmailcom.
If you have questions, topics,you want us to cover anything of
the sorts, we appreciate it andwe will catch everyone next
time.
See everyone, bye-bye.
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