December 10, 2025 • 34 mins
What if a child’s own tumor could teach their immune system how to fight back? We sit down with Dr. Liggon from the University of Florida to unpack a first‑in‑kids, personalized mRNA lipid nanoparticle therapy designed for high‑grade glioma and osteosarcoma. Instead of chasing a single target, this approach isolates mRNA directly from each patient’s tumor and packages it into lipid nanoparticles, training the immune system against a wide range of cancer proteins. That personalization is the point: every dose is built for one child, aiming to overcome the limits of one‑size‑fits‑all immunotherapy.
We walk through the basket trial design and why starting with these two cancers matters, especially when relapse rates are high and outcomes are poor. Dr. Liggon shares early adult data from glioblastoma patients showing rapid immune activation within hours—fevers, chills, and transient hypotension—signs that the therapy is doing its job without dose‑limiting toxicities. We also get practical: the six‑week manufacturing timeline from tumor to vaccine, the use of radiation or a non‑specific priming LNP to bridge that gap, and how the team measures pharmacodynamic markers at two and six hours to understand dose response over repeated treatments.
Collaboration is the backbone of this work. Our PICU team partners closely with oncology and immunotherapy colleagues to deliver infusions safely, manage inflammatory side effects, and collect the data that will refine dosing and duration. Behind the scenes, a funding story comes to life: local seed backing from Stop Children’s Cancer of Gainesville sparked momentum that grew into support from the V Foundation, National Pediatric Cancer Foundation, Alex’s Lemonade Stand Foundation, and the National Cancer Institute. Looking forward, the plan is to expand this platform to medulloblastoma, DIPG, Ewing sarcoma, and rhabdomyosarcoma as phase one findings guide the next steps.
Tune in to hear how personalized mRNA can move from lab to bedside, what signals we’re tracking, and where this platform could go next. If this resonates, follow the show, share it with a colleague, and leave a review with the questions you want us to ask in future updates.
Please take the survey using the link below:
https://ufl.qualtrics.com/jfe/form/SV_8whTtydadAMpx7o
References:
Kline-Tilford, A. M., & Haut, C. (2020). Cases in pediatric acute care: Strengthening clinical decision making. Wiley-Blackwell.
Additional Resources:
PICU Essentials on the App Store (apple.com)
PICU Essentials - Apps on Google Play
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Transcript
Episode Transcript
Available transcripts are automatically generated. Complete accuracy is not guaranteed.
SPEAKER_05 (00:22):
Welcome to the Gator Pick You podcast where pediatric
critical care is real worldlearning.
Whether you're grabbing coffee,charting at the bedside, on
shift, or on the go, we've gotyou covered.
Our episodes are short, focused,and designed to keep you sharp,
informed, and inspired.
Let's get into it.
SPEAKER_04 (00:41):
Dr.
Ligan is an assistant professorin the Department of Pediatrics
here at the University ofFlorida.
He is currently leading agroundbreaking clinical trial
testing a personalized mRNAlipid nanoparticle therapy.
Correct?
Yes.
Yes.
Absolutely.
(01:02):
Or RNALP for Dr.
Liggan, or excuse me, forchildren and young adults with
high-grade gliomas andosteosarcomas.
So Dr.
Liggan, thank you so much forbeing here.
If you want to go ahead andintroduce yourself and give us a
little background.
SPEAKER_01 (01:19):
Yeah, thank you so much.
I'm happy to be here and talk toyour listeners about our
platform.
As you said, I've uh I'm anassistant professor at the
University of Florida.
I came here about three and ahalf years ago and was recruited
to work with my mentors, um,Elias Sayer, Dwayne Mitchell,
and their immunotherapy group tohelp bring some of these new
(01:42):
immunotherapies forward forpatients with very difficult to
treat types of cancers andhopeful that we will find a new
treatment that will help themovercome their cancer.
SPEAKER_04 (01:53):
That's incredible.
Very good.
And Alyssa, do you want tointroduce yourself?
SPEAKER_03 (01:57):
Hi, my name is Alyssa Hood.
I am a nursing professionaldevelopment specialist with
nursing education focusing onthe pediatric and women's units.
SPEAKER_04 (02:05):
And my name is Amanda Bradshaw, and I'm a
clinical leader here in RPICU.
And I uh help with quality uhimprovement projects here as
well.
So, Dr.
Ligan, we're gonna go ahead andum get started with the big
picture.
So, what makes this new clinicaltrial so innovative?
SPEAKER_01 (02:26):
Yeah, so I I think what makes this really
innovative is that this is youknow trying to make a treatment
um or a type of treatment thathasn't worked for pediatrics in
the past, namely immunotherapy,which is trying to train the
body's immune system torecognize and fight cancer, um,
(02:47):
we're trying to make thateffective for pediatric cancers,
which it has not been effectivein the past.
And so we're hopeful that thisum new type of immunotherapy may
be successful for pediatriccancers that have not uh
previously responded toimmunotherapy.
In terms of the overall clinicaltrial, I think another thing
(03:09):
that's very exciting about thisis that we call this um a basket
trial.
And what I mean by that is thatit's it's not something that's
for just one kind of cancer,like bone cancer or brain cancer
or kidney cancer.
It's really a type of clinicaltrial where you could enroll
(03:29):
patients with many differentkinds of cancers and see for any
specific kind of cancer, do yousee signs that it's safe and
potentially effective for thesekinds of patients?
And so we're using this baskettrial to test this new
technology that was developed atthe University of Florida over
the last 10 years called mRNAlipid nanoparticle technology,
(03:54):
um, which we are using againstmultiple kinds of pediatric
cancers.
And right now we're evaluatinghow safe it is and how well it
can activate the immune systemin children with two specific
kinds of cancers.
One is a brain cancer calledhigh-grade glioma, and one of
them is a bone cancer calledosteosarcoma.
SPEAKER_04 (04:12):
Wow, wow, that's fascinating.
Um so for listeners who may notbe familiar, what exactly is
RNA-lp and how does it work?
SPEAKER_01 (04:23):
Yeah, so um the RNA-lp uses a version of mRNA
technology where we package thethe um kind of building blocks
of the cancer called mRNA insideof lipid nanoparticles, similar
to what people might know fromthe COVID-19 vaccines.
(04:44):
Um what's unique in our approachis that this is really a
personalized um treatment usingour RNA lipid nanoparticles.
Um we create a custom mRNAtherapeutic from the patient's
own tumor cells.
Then using our engineereddelivery system, we essentially
um encapsulate that mRNA in away that we think the body will
(05:08):
recognize this uh cancerbuilding block, the mRNA, as
being dangerous and allow us toreprogram the immune system so
the immune cells can moreeffectively recognize and attack
the cancer.
SPEAKER_03 (05:22):
Okay.
So that means each individuallike r RNA LP that they're
getting is made for thatpatient.
It's not a generic thing thatthey're getting.
Oh wow.
Okay, exactly.
So you're taking what they have,reusing it, and making this so
they can then fight the cancer,hopefully.
SPEAKER_01 (05:39):
Exactly.
And I think eventually we wouldlove to make kind of a you know,
quote unquote off-the-shelfvaccine that would work for
anybody.
And that's you know, a big um,you know, kind of part of our
ongoing research, you know, backin the lab.
Um, but right now what we'redoing in the clinical trial is
we're actually going in andwe're taking a pay a piece of
(06:02):
that patient's tumor andisolating isolating the mRNA
directly from the tumor.
SPEAKER_02 (06:08):
Okay.
SPEAKER_01 (06:09):
So it really is personalized.
Like so the what I'm giving backto that patient um could only
have been made from thatpatient's own tumor.
SPEAKER_04 (06:18):
Exactly.
Oh, okay.
I did not know that part ofthat.
I thought this was more of anon-specific.
An off-the-shelf, like you weresaying.
Yeah, non-specific.
Okay, very interesting.
Okay.
SPEAKER_03 (06:29):
Okay.
That's triggered a lot morequestions now.
So you talked about this as newin pediatrics.
What have we done, whetheroverall or specifically you have
health, what have we done foradults that's similar to this?
SPEAKER_01 (06:41):
Um, yeah.
So anytime that you're bringingforward a clinical trial for
children, um, almost all of thetime you have to do some sort of
testing in adult patients firstto make sure that at least it's
safe in adult patients beforeyou bring it to a vulnerable
population like children.
Right.
Um, and so we've followed thatum that pathway here as well,
(07:05):
um, and have treated severaladult patients now with a
essentially fatal brain tumorcalled glioblastoma.
Um and in the first ever humanclinical trial using the RNA LP,
we've treated now several adultpatients who've gotten the
treatment.
And what we've seen so far isthat they have rapid activation
(07:25):
of their immune system againstglioblastoma.
Um, we see that the immune cellsmove around very quickly within
like two to six hours within thepatient's body.
And we start seeing um signs ofinflammation in the patients as
well, in terms of like theydevelop fevers, they develop uh
(07:47):
you know, lower blood pressures,they develop chills.
And I say these things that eventhough they sound a little bit
scary, in some ways it'sencouraging to us as the um the
um team taking care of thepatient because it tells us that
the that our therapeutic isactivating the immune system.
(08:08):
All these things, fever, chills,it's signs of the immune system,
you know, getting revved up.
SPEAKER_04 (08:14):
Like a desired, uh, a desired effect.
Exactly.
SPEAKER_01 (08:18):
Right.
With it's we know that theimmune cells that are in the
patient are um you know kind ofgetting activated, and we're
hoping they're getting activatedagainst that patient's cancer.
Um so uh having given that toseveral adult patients now, um,
you know, we've seen that yes,it has these biological effects
(08:40):
that are leading to symptoms,um, but it hasn't caused any um
toxicity that we call adose-limiting toxicity, which is
like so severe that you can'tkeep giving the treatment to the
patient.
Um so having seen that it hasbeen um safe in the adult
patient so far, along with thesesigns that it's activating the
(09:03):
immune system, we've now uhdecided to move this um into
pediatric clinical trials.
And I should also mention thatbefore we brought this to
adults, we did a lot of otherpreclinical testing in mice and
actually in dogs as well.
Not you know, not like we wereuh giving the dogs cancer, but
(09:26):
uh it uh you know regular petdogs, osteosarcoma is actually
very common.
Brain tumors are very common.
And so pay um owners of petswhose uh pets developed a cancer
would bring their uh dogs to thevet school and enroll on the
veterinary clinical trials.
(09:46):
So this was the um, you know,kind of the the um building
blocks of evidence that we youknow generated to show that
there's a chance this may reallywork against real cancer before
we brought this forward to umreal human patients.
SPEAKER_04 (10:03):
Wow, that is wow, so great.
That's such a huge step.
That had to have been reallyreassuring to see.
SPEAKER_01 (10:10):
It was.
I mean, and uh yeah, there'sbeen a lot of work um testing
new cancer treatments in mice.
Um, I think being able to testit in um veterinary clinical
trials is something that'sactually really unique to the
University of Florida.
Because I mean, I can walk youknow 20 minutes down Archer Road
(10:33):
and make it to the Vet School.
And it just allows this level ofcollaboration that I you know
haven't seen at other uminstitutions.
SPEAKER_04 (10:41):
Right.
Yeah, an additional resource.
Yeah.
That's awesome.
SPEAKER_03 (10:44):
So I'm I'm interested that you said it you
start noticing symptoms two tosix hours, which symptoms are
good in this sense because itshows that your body's you know
kind of working against what youput in.
SPEAKER_01 (10:54):
We hope they are.
Right.
But yes.
SPEAKER_03 (10:56):
I feel like I want to ask the question of what was
the end result already.
I'm already like interested inhow I know we're not there yet,
but I'm so interested to seelike how it progressed with
adults and then how it'sprogressing.
SPEAKER_04 (11:08):
So presumably this is something that they will
receive over and over again.
So does the if they're having aninflammatory response, does that
build?
Does it get worse each time?
SPEAKER_01 (11:22):
That's a really great question.
And I think to both of yourpoint, it's something that we're
really working to understand.
Okay.
Yeah, and and any time thatwe're running a clinical trial,
um, especially phase one, neverbeen, you know, used in uh
humans, never been used inpediatrics.
It's our obligation as umresearchers not to just find
(11:46):
out, does this work or does thisnot work?
That's gonna take years to findout.
You'll you'll need to see, youknow, are these patients
remaining free from theircancer?
Um, but we also need to do a lotof work along the way to see,
you know, why is it working oris it not working?
That way, if it's not working,we can go back to the lab, we
(12:07):
can uh try to um change aroundour formulations, figure out how
to make um it work or overcomethe limitations of the first
design.
Because this is the firstdesign.
Right.
Like the chances that we'regoing to go, you know, with our
you know, first design,obviously we hope it's going to
work.
Of course.
(12:27):
Um, you know, we wouldn't givesomething to a patient if we
didn't think that there was achance that it would help them.
But if it doesn't, you know, weneed to learn from that
patient's.
SPEAKER_03 (12:38):
That's the point of the trial to kind of figure out
what the best option is.
Exactly.
SPEAKER_01 (12:42):
Um to at to really answer your question, it will
take longer to you know kind ofsee what these patients'
long-term outcomes are.
But I will say that we're ableto take um, you know, the
patient's blood at multiple timepoints after giving each of
these vaccines.
So we draw blood at two hoursafter the um the uh the
(13:06):
treatment, and then six hoursafter the treatment, and we're
able to see kind of how the umthe activation markers change on
those immune cells at thosedifferent times.
And then we're able to compare,okay, after the third treatment,
how does that compare to youknow after the first treatment?
Do we see a stronger immunologicresponse?
If it's getting stronger, youknow, can we actually back off a
(13:29):
little bit on the dose so thatour patients are not gonna have
such a significant uminflammatory response?
Okay.
Very interesting.
Yeah.
SPEAKER_03 (13:37):
Because either way, you have data now to then move
forward in whatever directionyou need to move forward in
since you have been able totrial it.
So that's always exciting.
SPEAKER_01 (13:45):
Exactly.
Yeah.
And that's all we want to do isum, you know, do what's best for
the patient that's right infront of us, but also help us to
better understand how to give itto the next patient as well.
SPEAKER_04 (13:57):
Interesting.
Wow.
So you talked about phase one alittle bit.
So let's let's kind of dive intolike what does phase one, phase
two, what are we focusing onwith this?
SPEAKER_01 (14:06):
Yeah.
So anytime that you're talkingabout different phase uh phases
of clinical trials, phase one isthe earliest phase, and phase
three is the you know, kind oflike latest phase.
Okay.
Phase one means that you're justtrying to find out, is this safe
and can I actually feasibly givethis treatment to a patient?
(14:27):
Okay.
Um and so usually in phase one,you're testing several different
doses of the treatment to see umis it safe at the lowest dose?
If yes, you can try a higherdose.
If it's still safe, you can goto the higher dose.
You're trying to find like whatis the highest dose that you can
give without causing those doselimiting toxicities that I
talked about earlier.
(14:48):
Once you find the right dose,then you can move into phase
two, which really answers thatquestion of is there a sign that
this treatment might beeffective against this kind of
cancer?
And if the answer there is yes,in a relatively small trial,
we're talking about like tens toon the high end, maybe a hundred
(15:09):
patients, and I don't thinkwe'll do that for uh pediatric
cancers, but um, if there's asignal that it might be
effective in phase two, that'swhen um you know you would
really think about like a largemulti-center hundreds of
patients clinical trial.
Um uh, you know, then that wouldbe a phase three confirmatory uh
(15:30):
clinical trial.
We're still very much in phaseone.
Sure.
Okay.
Um and it'll take us some timeto get through phase one, it'll
take us some time to get throughphase two.
Um, you know, so I think we'rewe're a ways off from you know a
definitive phase three study.
Okay.
Um and we're still very muchtrying to figure out what's the
right dose of this uh newtreatment.
SPEAKER_04 (15:49):
So is each dose, each dose is gonna be contingent
on each patient?
Considering it's madespecifically for them?
SPEAKER_01 (15:59):
Um so when I talk about the dose in this context,
I'm talking about like theamount of RNA that's being
given.
I see.
Um And so um when we'reenrolling new patients on the
trial, like three patients in arow will be given a certain dose
of RNA.
And then if that is deemed to besafe, then we increase the
amount of RNA for the next setof patients and so on and so
(16:21):
forth.
SPEAKER_03 (16:22):
Oh, excuse me.
Okay.
So you're at phase one for thepediatric trial.
SPEAKER_01 (16:27):
We're still in technically in phase one as well
for the adults.
Okay.
Although they're further alongin like a phone.
SPEAKER_03 (16:32):
Okay, that's what I was wondering.
Okay, so we really don't knowwhat the phase two, phase three
is even gonna lead towards yet.
So we're definitely in the stillfiguring out what the how it's
gonna go.
Let's say it's right.
SPEAKER_01 (16:44):
And uh yeah, I think we're a little closer to you
know starting phase two in theadults.
But um even the progress isamazing.
SPEAKER_03 (16:51):
Yeah.
I agree.
You know, I think it's a greatstep to an answer in some
regard, hopefully, of I I justhope that that's what it leads
to.
I think that's what we all hopethat it leads to.
SPEAKER_04 (17:00):
Yeah, and I think it's easy to get really excited
about something like that, youknow, especially because I did I
there was a headline onsomething in the elevator
corridor about the theveterinary clinic having uh
success with it.
And so um, so I think it's justexciting to kind of see it
translate over into the humanworld.
SPEAKER_03 (17:21):
And I think working in the PICU and seeing patients
firsthand, I think also gives usa different perspective and
almost makes me even moreexcited because you've seen the
not great side.
Yeah.
And so I think we want an answerso badly that it's easy to
really get kind of excited,emotional about it because you
(17:41):
just want an answer.
Right.
I mean, and we're hoping we'rethankful that for people like
you that are able to do thesethings and want to do these
things to help other patientsand kids, especially, but
anybody.
So it's really neat.
SPEAKER_01 (17:51):
Right.
And I I just want to reallyhighlight something that you
said there, uh which was youknow that the fact that we're
able to give this treatment andthe PICU.
And I I think that that speaksto a level of collaboration with
our intensivists, you know, hereat the University of Florida.
Um, that yeah, I I it's not likethere are no collaborations
(18:12):
anywhere else.
Right.
But I've found it, you know,really um you know gratifying to
work with the intensivists andthe entire team here because you
know, you guys, you know, we'rehere at this um, you know, big
academic setter, we do see a lotof bad outcomes for a lot of
different indications.
And you know, our charge reallyas um an academic institution is
(18:38):
how are we gonna move the barfor all of our patients?
Right.
And if that means that you knowwe have to, you know, find a way
to admit our patients to thePICU to you know manage a lot of
this, uh, these side effectsthat I just mentioned, you know,
the the fevers, chills, lowblood pressure, things like
that.
Um I'm really gratified thatwe've been able to work together
(19:00):
in a way that um you know makesthis really seamless for our
patients.
SPEAKER_02 (19:03):
It's awesome.
SPEAKER_03 (19:04):
I think we feel the same.
I think that we've whether it'syour team, whether it's another
research team that we've youknow used and seen up in the
PICU, I think we've, as theirresearch grows, we see them more
frequently.
And it's very interesting.
You get to know them, you talkto them about what what's going
on and new things that arehappening.
So it is, it definitely growsfrom a small collaboration to a
very big collaboration veryquickly, which is really nice
and really interesting to be apart of.
SPEAKER_04 (19:26):
And I think it's really helpful, it's uh very
special to see somebody verypassionate or a team who's very
passionate, especially aboutsomething so specific or niche
or whatever.
Um because I think it helps A,it helps when you're passionate
about something, you're gonnahelp deliver that information.
So you help educate thesepeople.
But sometimes you spark apassion within somebody else to
(19:49):
also be um a part of thatchange.
And so that's really special.
We're excited.
So um why were high gradegliomas and osteosarcus?
The chosen uh cancers?
SPEAKER_01 (20:03):
Yeah, that's a a a really great question.
Um and I think um you know uhthere are a couple of reasons
for one, both are extremelydifficult to treat when they
return.
Okay.
Um, you know, so essentially umfor a patient um uh with
osteosarcoma when it spreadsbeyond the the initial bone
(20:26):
site, um especially to thelungs, um less than 25% of
patients are gonna be stillalive at five years later.
For patients with thesehigh-grade gliomas, these
account for over um for ouralmost half of brain and spinal
cord tumors in children.
Um and if they don't respond tothe upfront treatment, which is
(20:48):
surgery and radiation therapy,it's essentially an incurable
cancer.
Um so we urgently need newtreatments for these patients
with brain tumors and with bonetumors.
Um and uh at least in ourpreclinical testing, these were
two pediatric cancers that hadthe strongest level of um uh you
(21:13):
know preliminary findings, bothin mice and in uh the canine
trials, um, that they umsupported us in moving it
forward for these um pediatriccancers.
SPEAKER_04 (21:25):
It's almost like a call to action.
Exactly.
SPEAKER_03 (21:30):
That's amazing.
Yeah, I'm just fascinated.
It is fascinating.
Um we did talk about the wetalked about the personalized
nature of this therapy.
So what does that mean forfamilies?
Like how does this all sortstart for them, the process of
that for the families and forthe patients?
SPEAKER_01 (21:49):
Yeah, so I I think again, that's one of the really
exciting things about thistreatment is that it's something
that's built specifically forthat one patient that's in front
of you.
So every child that receivesthis treatment is getting a
therapy that's builtspecifically from their own
tumor cells instead of a onesize fits all approach.
And so the RNA lipidnanoparticle, it we use that to
(22:11):
teach their immune system whattheir own unique cancer looks
like and how to respond to that.
Um so it really allows us tomove from other kinds of um
other kinds of immunotherapythat um, you know, while they
they could be effective, theyhave not in pediatrics.
And I think in large partbecause they're only going after
(22:34):
one type of protein that may beexpressed on the cancer.
Here by taking all of the mRNA,we can uh theoretically train
the immune system against all ofthe proteins that are in that
patient's cancer.
And so you have many moreopportunities to train the
immune system against differentproteins that are dangerous.
(22:54):
Um and hopefully if you'retargeting many different
proteins instead of just one, itoffers the um immune system more
targets and gives the canceraless uh chances to kind of evade
a um immune attack against justone protein because you're kind
of hitting it from everydifferent possible angle all at
(23:16):
once.
SPEAKER_04 (23:17):
Okay.
That's it's a good way to kindof think about, you know, um,
you know, trying to picture itfor people who are not as
specialized.
unknown (23:26):
Yeah.
SPEAKER_03 (23:27):
But I like yes, though instead of just the one
protein, you've got them allkind of over the place, which
makes sense of how it's able totarget it more specifically.
Yeah.
Okay.
SPEAKER_04 (23:36):
Um so f funding uh innovative pediatric research is
always challenging.
We have probably all experiencedthat to some degree.
So who is who's the one or whoare supporting um this the
development of this trial?
SPEAKER_01 (23:54):
Yeah, so that's one another place that I think we've
been very fortunate to have alot of support because as you
mentioned, um the it's it'schallenging to you know get
funding to um develop newtreatments, let alone run early
phase clinical trials.
So this trial grew um from achallenge grant from the Stop
Children's Cancer Foundation ofGainesville.
(24:16):
And they basically said that youknow, we're gonna give you this
money to develop this newtreatment for kids with
osteosarcoma.
Um and your charge is thatwithin X number of years, we
want you guys to be in a humanclinical trial.
And we we met that goal.
And their support um helped usto create this therapeutic, and
(24:37):
we've now expanded that you knowto multiple tumor types.
And as a result of receivingthat um, you know, initial seed
funding from STOP and from otheruh um foundations, you know,
we've been able to then generatethe preliminary data that
allowed us to get additionalfunding um from um other
(24:58):
organizations like the VFoundation, the National
Pediatric Cancer Foundation,Alex's Lemonade Stand
Foundation, and uh even theNational Cancer Institute.
So getting that like initialseed funding from um local
organizations that believe inour vision has really been
critical to allowing us togetting that follow-on funding
(25:21):
because it allowed us to get tostart the process.
And once you start the process,you can build momentum and we're
hoping that we can keep thatmomentum going.
SPEAKER_04 (25:29):
Wow, that's incredible.
SPEAKER_03 (25:31):
I think that this is my own thought for a second.
I think that when we work here,we see and we we're working
every day, we're doing thoserepetitive things, but then to
hear you talk about that andthat you're getting this and how
large this is getting, you thesupport that you're getting, the
fun you're getting from NationalCancer Institutes, things like
that is just kind ofmind-boggling.
(25:52):
Because we we're here every daydoing it.
And then to hear how far ourhospital our little hospital is
getting is crazy to think about.
It's not a little hospital, butyou know what I mean?
Like our home is getting so big,it's just in so interesting to
think about.
SPEAKER_04 (26:06):
Well, and I think especially for people like us
who are raised here and and youknow, this has, you know, I
think when you're so close to apicture, it's hard to see the
full view.
And so sometimes when you comein day in, day out, you clock
in, you clock out, uh, you don'tget to see the biggest part of
the picture.
SPEAKER_03 (26:24):
And the impact that we're really hacking and that
you uh your team is reallymaking, which is very
interesting to hear about.
SPEAKER_01 (26:28):
Yeah, no, I mean, and again, we couldn't do it
without um a team that believesin the mission of developing,
you know, newer and bettertreatments for patients.
And I think that that's that'swhy a lot of us we want to be in
academics.
We want to be where we're movingthe the bar.
You know, like of course we wantto help, you know, the the
(26:51):
four-month-old who's coming inwith bronchiolitis and you know
needs their support.
And you know, we have to be areferral center for that.
But you know, we we also um youknow really have an obligation
that if we're doing all thiscool stuff in the lab, you know,
developing mRNA therapeutics, weneed to make sure that we're
going to actually bring thisforward to patients and find out
(27:14):
definitively.
Is this gonna work for patients?
Yes or no.
And um I'm I'm glad that we'reat an institution um where we're
able to collaborate across uhmultiple teams um to deliver
this kind of care safely for ourpatients and get these answers
to the questions that peoplereally across the entire country
(27:34):
are asking and want to know.
SPEAKER_04 (27:36):
Yeah.
And I I'm eager, you know, yes,to see where this heads.
Me too.
So so looking ahead in all ofthis, do you expect this trial
to expand out to even morecancers?
SPEAKER_01 (27:49):
Yeah, absolutely.
So our long-term goal is to addadditional trial arms uh using
this RNA-lipid nanoparticleplatform to create personalized
immunotherapies for other umtypes of relapsed or difficult
to peak difficult to treatpediatric cancers.
Um, and that includes othertypes of pediatric brain tumors
like medulloblastoma, diffuseintrinsic pontine glioma, and
(28:12):
other sarcomas like ewingsarcoma, rhabdomyar sarcoma.
Um, so I I anticipate that we'regoing to open you know more
trials you know in the future aswe gain additional um experience
with these first two kinds ofcancers that we've been
treating.
SPEAKER_04 (28:28):
Excellent.
Wow.
SPEAKER_03 (28:30):
Uh I mean it is.
It's a very And I know we're inphase one, so it's it's under I
think we have a lot of hope anda lot of encouragement, but
we're in phase one.
We're trying, we're gonna, youknow, go with the trial and
follow the trial and and workour way to all those other steps
and all those other phases.
SPEAKER_04 (28:45):
It just But I think when you've been, you know, I've
been in nursing for a reallylong time.
Right.
And I think sometimes, again,you kind of just get blinded by
the the day-to-day.
And so to see something so bigand to know that you know, maybe
like the up-and-coming kids thatare going, you know, in high
(29:06):
school right now, they're gonnago to college and they're gonna
grow, they're not in.
So I think there's just so muchum prospect for what could
happen.
And I think that's it's it'svery exciting.
SPEAKER_03 (29:18):
So I did have one other question that kind of
popped up.
How long this is how long doesit take from you to get the
sample from the tumor to makingthe actual mRNA vaccine for
them?
How long does that process take?
SPEAKER_01 (29:31):
That's a great question.
And that's actually reallyimportant for our trials because
uh I didn't fully get into kindof how long that takes and what
we do while we're making thetreatment.
Um, but so it takes aboutsix-ish weeks from when we take
the tumor out of the patient uhto making the um the lipid
(29:53):
nanoparticle.
Um and so that gives likethere's a gap there of about six
weeks where you have a patientwho still has cancer and needs
to be treated.
Um and so for some of ourclinical trials, if it's a newly
diagnosed patient, what we'reable to do is we're able to give
them the kind of normalradiation treatment that um we
(30:14):
uh we might uh be giving asstandard of care.
Um and so that gives a goodlittle bridge to get to the
patient's personalized lipidnanoparticle.
For patients where we'retreating them when the cancer
has come back or it's recurred,um what we do there is we
actually do use an off-the-shelfum, you know, lipid nanoparticle
(30:37):
because we think that using thisnon-specific um uh peptide uh
based lipid nanoparticle, whileit may not be specific for that
patient's cancer, we have shownin uh some of our preclinical
testing that it can actuallystart the process of priming the
immune system.
We're starting to reprogram umthe immune system so that way
(31:02):
when we give the personalizedtreatment, it may respond even
better than a a patient thatdidn't get that those priming
doses.
SPEAKER_03 (31:10):
So at least help it it helps bridge that gap, like
you were saying, at least forthose six weeks where you're
kind of waiting.
SPEAKER_01 (31:15):
Exactly.
That's the that's the hypothesisum or you know, kind of our our
thought process right now.
Um I think um, you know, we'llkind of have to you know see how
that goes.
SPEAKER_04 (31:26):
Right.
Wow.
Interesting.
Is there um this just kind ofstimulated a question for me?
Uh is there a length oftreatment for the for the um uh
mRNA?
SPEAKER_01 (31:39):
That's another great question that we're trying to
answer.
Okay.
Um so at least like right now,you know, we're uh we're
thinking like, you know, let'stry giving it over a whole year.
Okay.
Um because we we don't reallyknow like um after we give the
lipid nanoparticle, how long isthe immunity that you induce
(32:00):
against the patient's tumorgonna last?
Is it gonna stick around for sixmonths?
Is it gonna stick around for onemonth?
Is it gonna stick around for 24hours?
You know, I I'm not entirelysure.
And yeah, like to your pointearlier, the the other question
is like, do you get kind of anamplification of the um immune
response with more treatmentsthat you give?
(32:21):
If you give three nanoparticles,is that enough to teach the body
to permanently recognize uh thecancer?
Do you need to give it for awhole year to give it durable
immunity or to at least um keepthe immune system activated long
enough to wipe up any lastremaining tumor cells that are
(32:42):
there?
We're not sure.
We know that we can make um youknow enough of the lipid
nanoparticles to last for awhole year.
Um whether they need to get itfor that long, or if we can you
know kind of cut it off afteryou know three or five or
whatever arbitrary number ofdoses, um, I think that's an
open question as well.
SPEAKER_03 (33:03):
Okay, interesting.
So still things to learnobviously there's still things
to learn.
Okay.
Yes.
Wow.
SPEAKER_04 (33:08):
Wow, yep.
So, Dr.
Ligan, thank you so much uh foryour work and for kind of taking
your time to come and talk withus today to explain all of this.
This has been fascinating.
Um this trial represents anexciting new chapter, obviously,
in pediatric cancer and the carefor those kiddos and their
families.
(33:28):
And we obviously will bewatching and cheering for you
guys very much as the rest ofthis unfolds.
Um, do you have any parting, anyparting words you want to share
with us?
SPEAKER_01 (33:40):
Yeah, just again, I'm I'm so thankful for the
collaboration, you know, withthe the PICU.
Uh, you know, we wouldn't, youknow, feel as confident as we do
about moving this treatmentforward if we didn't know that
you guys were watching over ourpatients with a you know very
watchful eye and ready tointervene with any um toxicity.
(34:00):
And um I think that really onlyby having a great team that is
fully invested can we move newtreatments forward like this
safely and really answer theimportant questions that we're
all asking.
Excellent.
SPEAKER_03 (34:16):
Wow.
Well, thanks everyone forjoining us in the Gator Picky
podcast.
And we will see you next time.
Thank you, Dr.
Ligan.
We really appreciate it.
SPEAKER_04 (34:24):
It's been wonderful.
Yes.
SPEAKER_01 (34:26):
Thank you guys very much.
At least I managed to set up.
Welcome to the Gator Pick You podcast where pediatric
critical care is real worldlearning.
Whether you're grabbing coffee,charting at the bedside, on
shift, or on the go, we've gotyou covered.
Our episodes are short, focused,and designed to keep you sharp,
informed, and inspired.
Let's get into it.
SPEAKER_04 (00:41):
Dr.
Ligan is an assistant professorin the Department of Pediatrics
here at the University ofFlorida.
He is currently leading agroundbreaking clinical trial
testing a personalized mRNAlipid nanoparticle therapy.
Correct?
Yes.
Yes.
Absolutely.
(01:02):
Or RNALP for Dr.
Liggan, or excuse me, forchildren and young adults with
high-grade gliomas andosteosarcomas.
So Dr.
Liggan, thank you so much forbeing here.
If you want to go ahead andintroduce yourself and give us a
little background.
SPEAKER_01 (01:19):
Yeah, thank you so much.
I'm happy to be here and talk toyour listeners about our
platform.
As you said, I've uh I'm anassistant professor at the
University of Florida.
I came here about three and ahalf years ago and was recruited
to work with my mentors, um,Elias Sayer, Dwayne Mitchell,
and their immunotherapy group tohelp bring some of these new
(01:42):
immunotherapies forward forpatients with very difficult to
treat types of cancers andhopeful that we will find a new
treatment that will help themovercome their cancer.
SPEAKER_04 (01:53):
That's incredible.
Very good.
And Alyssa, do you want tointroduce yourself?
SPEAKER_03 (01:57):
Hi, my name is Alyssa Hood.
I am a nursing professionaldevelopment specialist with
nursing education focusing onthe pediatric and women's units.
SPEAKER_04 (02:05):
And my name is Amanda Bradshaw, and I'm a
clinical leader here in RPICU.
And I uh help with quality uhimprovement projects here as
well.
So, Dr.
Ligan, we're gonna go ahead andum get started with the big
picture.
So, what makes this new clinicaltrial so innovative?
SPEAKER_01 (02:26):
Yeah, so I I think what makes this really
innovative is that this is youknow trying to make a treatment
um or a type of treatment thathasn't worked for pediatrics in
the past, namely immunotherapy,which is trying to train the
body's immune system torecognize and fight cancer, um,
(02:47):
we're trying to make thateffective for pediatric cancers,
which it has not been effectivein the past.
And so we're hopeful that thisum new type of immunotherapy may
be successful for pediatriccancers that have not uh
previously responded toimmunotherapy.
In terms of the overall clinicaltrial, I think another thing
(03:09):
that's very exciting about thisis that we call this um a basket
trial.
And what I mean by that is thatit's it's not something that's
for just one kind of cancer,like bone cancer or brain cancer
or kidney cancer.
It's really a type of clinicaltrial where you could enroll
(03:29):
patients with many differentkinds of cancers and see for any
specific kind of cancer, do yousee signs that it's safe and
potentially effective for thesekinds of patients?
And so we're using this baskettrial to test this new
technology that was developed atthe University of Florida over
the last 10 years called mRNAlipid nanoparticle technology,
(03:54):
um, which we are using againstmultiple kinds of pediatric
cancers.
And right now we're evaluatinghow safe it is and how well it
can activate the immune systemin children with two specific
kinds of cancers.
One is a brain cancer calledhigh-grade glioma, and one of
them is a bone cancer calledosteosarcoma.
SPEAKER_04 (04:12):
Wow, wow, that's fascinating.
Um so for listeners who may notbe familiar, what exactly is
RNA-lp and how does it work?
SPEAKER_01 (04:23):
Yeah, so um the RNA-lp uses a version of mRNA
technology where we package thethe um kind of building blocks
of the cancer called mRNA insideof lipid nanoparticles, similar
to what people might know fromthe COVID-19 vaccines.
(04:44):
Um what's unique in our approachis that this is really a
personalized um treatment usingour RNA lipid nanoparticles.
Um we create a custom mRNAtherapeutic from the patient's
own tumor cells.
Then using our engineereddelivery system, we essentially
um encapsulate that mRNA in away that we think the body will
(05:08):
recognize this uh cancerbuilding block, the mRNA, as
being dangerous and allow us toreprogram the immune system so
the immune cells can moreeffectively recognize and attack
the cancer.
SPEAKER_03 (05:22):
Okay.
So that means each individuallike r RNA LP that they're
getting is made for thatpatient.
It's not a generic thing thatthey're getting.
Oh wow.
Okay, exactly.
So you're taking what they have,reusing it, and making this so
they can then fight the cancer,hopefully.
SPEAKER_01 (05:39):
Exactly.
And I think eventually we wouldlove to make kind of a you know,
quote unquote off-the-shelfvaccine that would work for
anybody.
And that's you know, a big um,you know, kind of part of our
ongoing research, you know, backin the lab.
Um, but right now what we'redoing in the clinical trial is
we're actually going in andwe're taking a pay a piece of
(06:02):
that patient's tumor andisolating isolating the mRNA
directly from the tumor.
SPEAKER_02 (06:08):
Okay.
SPEAKER_01 (06:09):
So it really is personalized.
Like so the what I'm giving backto that patient um could only
have been made from thatpatient's own tumor.
SPEAKER_04 (06:18):
Exactly.
Oh, okay.
I did not know that part ofthat.
I thought this was more of anon-specific.
An off-the-shelf, like you weresaying.
Yeah, non-specific.
Okay, very interesting.
Okay.
SPEAKER_03 (06:29):
Okay.
That's triggered a lot morequestions now.
So you talked about this as newin pediatrics.
What have we done, whetheroverall or specifically you have
health, what have we done foradults that's similar to this?
SPEAKER_01 (06:41):
Um, yeah.
So anytime that you're bringingforward a clinical trial for
children, um, almost all of thetime you have to do some sort of
testing in adult patients firstto make sure that at least it's
safe in adult patients beforeyou bring it to a vulnerable
population like children.
Right.
Um, and so we've followed thatum that pathway here as well,
(07:05):
um, and have treated severaladult patients now with a
essentially fatal brain tumorcalled glioblastoma.
Um and in the first ever humanclinical trial using the RNA LP,
we've treated now several adultpatients who've gotten the
treatment.
And what we've seen so far isthat they have rapid activation
(07:25):
of their immune system againstglioblastoma.
Um, we see that the immune cellsmove around very quickly within
like two to six hours within thepatient's body.
And we start seeing um signs ofinflammation in the patients as
well, in terms of like theydevelop fevers, they develop uh
(07:47):
you know, lower blood pressures,they develop chills.
And I say these things that eventhough they sound a little bit
scary, in some ways it'sencouraging to us as the um the
um team taking care of thepatient because it tells us that
the that our therapeutic isactivating the immune system.
(08:08):
All these things, fever, chills,it's signs of the immune system,
you know, getting revved up.
SPEAKER_04 (08:14):
Like a desired, uh, a desired effect.
Exactly.
SPEAKER_01 (08:18):
Right.
With it's we know that theimmune cells that are in the
patient are um you know kind ofgetting activated, and we're
hoping they're getting activatedagainst that patient's cancer.
Um so uh having given that toseveral adult patients now, um,
you know, we've seen that yes,it has these biological effects
(08:40):
that are leading to symptoms,um, but it hasn't caused any um
toxicity that we call adose-limiting toxicity, which is
like so severe that you can'tkeep giving the treatment to the
patient.
Um so having seen that it hasbeen um safe in the adult
patient so far, along with thesesigns that it's activating the
(09:03):
immune system, we've now uhdecided to move this um into
pediatric clinical trials.
And I should also mention thatbefore we brought this to
adults, we did a lot of otherpreclinical testing in mice and
actually in dogs as well.
Not you know, not like we wereuh giving the dogs cancer, but
(09:26):
uh it uh you know regular petdogs, osteosarcoma is actually
very common.
Brain tumors are very common.
And so pay um owners of petswhose uh pets developed a cancer
would bring their uh dogs to thevet school and enroll on the
veterinary clinical trials.
(09:46):
So this was the um, you know,kind of the the um building
blocks of evidence that we youknow generated to show that
there's a chance this may reallywork against real cancer before
we brought this forward to umreal human patients.
SPEAKER_04 (10:03):
Wow, that is wow, so great.
That's such a huge step.
That had to have been reallyreassuring to see.
SPEAKER_01 (10:10):
It was.
I mean, and uh yeah, there'sbeen a lot of work um testing
new cancer treatments in mice.
Um, I think being able to testit in um veterinary clinical
trials is something that'sactually really unique to the
University of Florida.
Because I mean, I can walk youknow 20 minutes down Archer Road
(10:33):
and make it to the Vet School.
And it just allows this level ofcollaboration that I you know
haven't seen at other uminstitutions.
SPEAKER_04 (10:41):
Right.
Yeah, an additional resource.
Yeah.
That's awesome.
SPEAKER_03 (10:44):
So I'm I'm interested that you said it you
start noticing symptoms two tosix hours, which symptoms are
good in this sense because itshows that your body's you know
kind of working against what youput in.
SPEAKER_01 (10:54):
We hope they are.
Right.
But yes.
SPEAKER_03 (10:56):
I feel like I want to ask the question of what was
the end result already.
I'm already like interested inhow I know we're not there yet,
but I'm so interested to seelike how it progressed with
adults and then how it'sprogressing.
SPEAKER_04 (11:08):
So presumably this is something that they will
receive over and over again.
So does the if they're having aninflammatory response, does that
build?
Does it get worse each time?
SPEAKER_01 (11:22):
That's a really great question.
And I think to both of yourpoint, it's something that we're
really working to understand.
Okay.
Yeah, and and any time thatwe're running a clinical trial,
um, especially phase one, neverbeen, you know, used in uh
humans, never been used inpediatrics.
It's our obligation as umresearchers not to just find
(11:46):
out, does this work or does thisnot work?
That's gonna take years to findout.
You'll you'll need to see, youknow, are these patients
remaining free from theircancer?
Um, but we also need to do a lotof work along the way to see,
you know, why is it working oris it not working?
That way, if it's not working,we can go back to the lab, we
(12:07):
can uh try to um change aroundour formulations, figure out how
to make um it work or overcomethe limitations of the first
design.
Because this is the firstdesign.
Right.
Like the chances that we'regoing to go, you know, with our
you know, first design,obviously we hope it's going to
work.
Of course.
(12:27):
Um, you know, we wouldn't givesomething to a patient if we
didn't think that there was achance that it would help them.
But if it doesn't, you know, weneed to learn from that
patient's.
SPEAKER_03 (12:38):
That's the point of the trial to kind of figure out
what the best option is.
Exactly.
SPEAKER_01 (12:42):
Um to at to really answer your question, it will
take longer to you know kind ofsee what these patients'
long-term outcomes are.
But I will say that we're ableto take um, you know, the
patient's blood at multiple timepoints after giving each of
these vaccines.
So we draw blood at two hoursafter the um the uh the
(13:06):
treatment, and then six hoursafter the treatment, and we're
able to see kind of how the umthe activation markers change on
those immune cells at thosedifferent times.
And then we're able to compare,okay, after the third treatment,
how does that compare to youknow after the first treatment?
Do we see a stronger immunologicresponse?
If it's getting stronger, youknow, can we actually back off a
(13:29):
little bit on the dose so thatour patients are not gonna have
such a significant uminflammatory response?
Okay.
Very interesting.
Yeah.
SPEAKER_03 (13:37):
Because either way, you have data now to then move
forward in whatever directionyou need to move forward in
since you have been able totrial it.
So that's always exciting.
SPEAKER_01 (13:45):
Exactly.
Yeah.
And that's all we want to do isum, you know, do what's best for
the patient that's right infront of us, but also help us to
better understand how to give itto the next patient as well.
SPEAKER_04 (13:57):
Interesting.
Wow.
So you talked about phase one alittle bit.
So let's let's kind of dive intolike what does phase one, phase
two, what are we focusing onwith this?
SPEAKER_01 (14:06):
Yeah.
So anytime that you're talkingabout different phase uh phases
of clinical trials, phase one isthe earliest phase, and phase
three is the you know, kind oflike latest phase.
Okay.
Phase one means that you're justtrying to find out, is this safe
and can I actually feasibly givethis treatment to a patient?
(14:27):
Okay.
Um and so usually in phase one,you're testing several different
doses of the treatment to see umis it safe at the lowest dose?
If yes, you can try a higherdose.
If it's still safe, you can goto the higher dose.
You're trying to find like whatis the highest dose that you can
give without causing those doselimiting toxicities that I
talked about earlier.
(14:48):
Once you find the right dose,then you can move into phase
two, which really answers thatquestion of is there a sign that
this treatment might beeffective against this kind of
cancer?
And if the answer there is yes,in a relatively small trial,
we're talking about like tens toon the high end, maybe a hundred
(15:09):
patients, and I don't thinkwe'll do that for uh pediatric
cancers, but um, if there's asignal that it might be
effective in phase two, that'swhen um you know you would
really think about like a largemulti-center hundreds of
patients clinical trial.
Um uh, you know, then that wouldbe a phase three confirmatory uh
(15:30):
clinical trial.
We're still very much in phaseone.
Sure.
Okay.
Um and it'll take us some timeto get through phase one, it'll
take us some time to get throughphase two.
Um, you know, so I think we'rewe're a ways off from you know a
definitive phase three study.
Okay.
Um and we're still very muchtrying to figure out what's the
right dose of this uh newtreatment.
SPEAKER_04 (15:49):
So is each dose, each dose is gonna be contingent
on each patient?
Considering it's madespecifically for them?
SPEAKER_01 (15:59):
Um so when I talk about the dose in this context,
I'm talking about like theamount of RNA that's being
given.
I see.
Um And so um when we'reenrolling new patients on the
trial, like three patients in arow will be given a certain dose
of RNA.
And then if that is deemed to besafe, then we increase the
amount of RNA for the next setof patients and so on and so
(16:21):
forth.
SPEAKER_03 (16:22):
Oh, excuse me.
Okay.
So you're at phase one for thepediatric trial.
SPEAKER_01 (16:27):
We're still in technically in phase one as well
for the adults.
Okay.
Although they're further alongin like a phone.
SPEAKER_03 (16:32):
Okay, that's what I was wondering.
Okay, so we really don't knowwhat the phase two, phase three
is even gonna lead towards yet.
So we're definitely in the stillfiguring out what the how it's
gonna go.
Let's say it's right.
SPEAKER_01 (16:44):
And uh yeah, I think we're a little closer to you
know starting phase two in theadults.
But um even the progress isamazing.
SPEAKER_03 (16:51):
Yeah.
I agree.
You know, I think it's a greatstep to an answer in some
regard, hopefully, of I I justhope that that's what it leads
to.
I think that's what we all hopethat it leads to.
SPEAKER_04 (17:00):
Yeah, and I think it's easy to get really excited
about something like that, youknow, especially because I did I
there was a headline onsomething in the elevator
corridor about the theveterinary clinic having uh
success with it.
And so um, so I think it's justexciting to kind of see it
translate over into the humanworld.
SPEAKER_03 (17:21):
And I think working in the PICU and seeing patients
firsthand, I think also gives usa different perspective and
almost makes me even moreexcited because you've seen the
not great side.
Yeah.
And so I think we want an answerso badly that it's easy to
really get kind of excited,emotional about it because you
(17:41):
just want an answer.
Right.
I mean, and we're hoping we'rethankful that for people like
you that are able to do thesethings and want to do these
things to help other patientsand kids, especially, but
anybody.
So it's really neat.
SPEAKER_01 (17:51):
Right.
And I I just want to reallyhighlight something that you
said there, uh which was youknow that the fact that we're
able to give this treatment andthe PICU.
And I I think that that speaksto a level of collaboration with
our intensivists, you know, hereat the University of Florida.
Um, that yeah, I I it's not likethere are no collaborations
(18:12):
anywhere else.
Right.
But I've found it, you know,really um you know gratifying to
work with the intensivists andthe entire team here because you
know, you guys, you know, we'rehere at this um, you know, big
academic setter, we do see a lotof bad outcomes for a lot of
different indications.
And you know, our charge reallyas um an academic institution is
(18:38):
how are we gonna move the barfor all of our patients?
Right.
And if that means that you knowwe have to, you know, find a way
to admit our patients to thePICU to you know manage a lot of
this, uh, these side effectsthat I just mentioned, you know,
the the fevers, chills, lowblood pressure, things like
that.
Um I'm really gratified thatwe've been able to work together
(19:00):
in a way that um you know makesthis really seamless for our
patients.
SPEAKER_02 (19:03):
It's awesome.
SPEAKER_03 (19:04):
I think we feel the same.
I think that we've whether it'syour team, whether it's another
research team that we've youknow used and seen up in the
PICU, I think we've, as theirresearch grows, we see them more
frequently.
And it's very interesting.
You get to know them, you talkto them about what what's going
on and new things that arehappening.
So it is, it definitely growsfrom a small collaboration to a
very big collaboration veryquickly, which is really nice
and really interesting to be apart of.
SPEAKER_04 (19:26):
And I think it's really helpful, it's uh very
special to see somebody verypassionate or a team who's very
passionate, especially aboutsomething so specific or niche
or whatever.
Um because I think it helps A,it helps when you're passionate
about something, you're gonnahelp deliver that information.
So you help educate thesepeople.
But sometimes you spark apassion within somebody else to
(19:49):
also be um a part of thatchange.
And so that's really special.
We're excited.
So um why were high gradegliomas and osteosarcus?
The chosen uh cancers?
SPEAKER_01 (20:03):
Yeah, that's a a a really great question.
Um and I think um you know uhthere are a couple of reasons
for one, both are extremelydifficult to treat when they
return.
Okay.
Um, you know, so essentially umfor a patient um uh with
osteosarcoma when it spreadsbeyond the the initial bone
(20:26):
site, um especially to thelungs, um less than 25% of
patients are gonna be stillalive at five years later.
For patients with thesehigh-grade gliomas, these
account for over um for ouralmost half of brain and spinal
cord tumors in children.
Um and if they don't respond tothe upfront treatment, which is
(20:48):
surgery and radiation therapy,it's essentially an incurable
cancer.
Um so we urgently need newtreatments for these patients
with brain tumors and with bonetumors.
Um and uh at least in ourpreclinical testing, these were
two pediatric cancers that hadthe strongest level of um uh you
(21:13):
know preliminary findings, bothin mice and in uh the canine
trials, um, that they umsupported us in moving it
forward for these um pediatriccancers.
SPEAKER_04 (21:25):
It's almost like a call to action.
Exactly.
SPEAKER_03 (21:30):
That's amazing.
Yeah, I'm just fascinated.
It is fascinating.
Um we did talk about the wetalked about the personalized
nature of this therapy.
So what does that mean forfamilies?
Like how does this all sortstart for them, the process of
that for the families and forthe patients?
SPEAKER_01 (21:49):
Yeah, so I I think again, that's one of the really
exciting things about thistreatment is that it's something
that's built specifically forthat one patient that's in front
of you.
So every child that receivesthis treatment is getting a
therapy that's builtspecifically from their own
tumor cells instead of a onesize fits all approach.
And so the RNA lipidnanoparticle, it we use that to
(22:11):
teach their immune system whattheir own unique cancer looks
like and how to respond to that.
Um so it really allows us tomove from other kinds of um
other kinds of immunotherapythat um, you know, while they
they could be effective, theyhave not in pediatrics.
And I think in large partbecause they're only going after
(22:34):
one type of protein that may beexpressed on the cancer.
Here by taking all of the mRNA,we can uh theoretically train
the immune system against all ofthe proteins that are in that
patient's cancer.
And so you have many moreopportunities to train the
immune system against differentproteins that are dangerous.
(22:54):
Um and hopefully if you'retargeting many different
proteins instead of just one, itoffers the um immune system more
targets and gives the canceraless uh chances to kind of evade
a um immune attack against justone protein because you're kind
of hitting it from everydifferent possible angle all at
(23:16):
once.
SPEAKER_04 (23:17):
Okay.
That's it's a good way to kindof think about, you know, um,
you know, trying to picture itfor people who are not as
specialized.
unknown (23:26):
Yeah.
SPEAKER_03 (23:27):
But I like yes, though instead of just the one
protein, you've got them allkind of over the place, which
makes sense of how it's able totarget it more specifically.
Yeah.
Okay.
SPEAKER_04 (23:36):
Um so f funding uh innovative pediatric research is
always challenging.
We have probably all experiencedthat to some degree.
So who is who's the one or whoare supporting um this the
development of this trial?
SPEAKER_01 (23:54):
Yeah, so that's one another place that I think we've
been very fortunate to have alot of support because as you
mentioned, um the it's it'schallenging to you know get
funding to um develop newtreatments, let alone run early
phase clinical trials.
So this trial grew um from achallenge grant from the Stop
Children's Cancer Foundation ofGainesville.
(24:16):
And they basically said that youknow, we're gonna give you this
money to develop this newtreatment for kids with
osteosarcoma.
Um and your charge is thatwithin X number of years, we
want you guys to be in a humanclinical trial.
And we we met that goal.
And their support um helped usto create this therapeutic, and
(24:37):
we've now expanded that you knowto multiple tumor types.
And as a result of receivingthat um, you know, initial seed
funding from STOP and from otheruh um foundations, you know,
we've been able to then generatethe preliminary data that
allowed us to get additionalfunding um from um other
(24:58):
organizations like the VFoundation, the National
Pediatric Cancer Foundation,Alex's Lemonade Stand
Foundation, and uh even theNational Cancer Institute.
So getting that like initialseed funding from um local
organizations that believe inour vision has really been
critical to allowing us togetting that follow-on funding
(25:21):
because it allowed us to get tostart the process.
And once you start the process,you can build momentum and we're
hoping that we can keep thatmomentum going.
SPEAKER_04 (25:29):
Wow, that's incredible.
SPEAKER_03 (25:31):
I think that this is my own thought for a second.
I think that when we work here,we see and we we're working
every day, we're doing thoserepetitive things, but then to
hear you talk about that andthat you're getting this and how
large this is getting, you thesupport that you're getting, the
fun you're getting from NationalCancer Institutes, things like
that is just kind ofmind-boggling.
(25:52):
Because we we're here every daydoing it.
And then to hear how far ourhospital our little hospital is
getting is crazy to think about.
It's not a little hospital, butyou know what I mean?
Like our home is getting so big,it's just in so interesting to
think about.
SPEAKER_04 (26:06):
Well, and I think especially for people like us
who are raised here and and youknow, this has, you know, I
think when you're so close to apicture, it's hard to see the
full view.
And so sometimes when you comein day in, day out, you clock
in, you clock out, uh, you don'tget to see the biggest part of
the picture.
SPEAKER_03 (26:24):
And the impact that we're really hacking and that
you uh your team is reallymaking, which is very
interesting to hear about.
SPEAKER_01 (26:28):
Yeah, no, I mean, and again, we couldn't do it
without um a team that believesin the mission of developing,
you know, newer and bettertreatments for patients.
And I think that that's that'swhy a lot of us we want to be in
academics.
We want to be where we're movingthe the bar.
You know, like of course we wantto help, you know, the the
(26:51):
four-month-old who's coming inwith bronchiolitis and you know
needs their support.
And you know, we have to be areferral center for that.
But you know, we we also um youknow really have an obligation
that if we're doing all thiscool stuff in the lab, you know,
developing mRNA therapeutics, weneed to make sure that we're
going to actually bring thisforward to patients and find out
(27:14):
definitively.
Is this gonna work for patients?
Yes or no.
And um I'm I'm glad that we'reat an institution um where we're
able to collaborate across uhmultiple teams um to deliver
this kind of care safely for ourpatients and get these answers
to the questions that peoplereally across the entire country
(27:34):
are asking and want to know.
SPEAKER_04 (27:36):
Yeah.
And I I'm eager, you know, yes,to see where this heads.
Me too.
So so looking ahead in all ofthis, do you expect this trial
to expand out to even morecancers?
SPEAKER_01 (27:49):
Yeah, absolutely.
So our long-term goal is to addadditional trial arms uh using
this RNA-lipid nanoparticleplatform to create personalized
immunotherapies for other umtypes of relapsed or difficult
to peak difficult to treatpediatric cancers.
Um, and that includes othertypes of pediatric brain tumors
like medulloblastoma, diffuseintrinsic pontine glioma, and
(28:12):
other sarcomas like ewingsarcoma, rhabdomyar sarcoma.
Um, so I I anticipate that we'regoing to open you know more
trials you know in the future aswe gain additional um experience
with these first two kinds ofcancers that we've been
treating.
SPEAKER_04 (28:28):
Excellent.
Wow.
SPEAKER_03 (28:30):
Uh I mean it is.
It's a very And I know we're inphase one, so it's it's under I
think we have a lot of hope anda lot of encouragement, but
we're in phase one.
We're trying, we're gonna, youknow, go with the trial and
follow the trial and and workour way to all those other steps
and all those other phases.
SPEAKER_04 (28:45):
It just But I think when you've been, you know, I've
been in nursing for a reallylong time.
Right.
And I think sometimes, again,you kind of just get blinded by
the the day-to-day.
And so to see something so bigand to know that you know, maybe
like the up-and-coming kids thatare going, you know, in high
(29:06):
school right now, they're gonnago to college and they're gonna
grow, they're not in.
So I think there's just so muchum prospect for what could
happen.
And I think that's it's it'svery exciting.
SPEAKER_03 (29:18):
So I did have one other question that kind of
popped up.
How long this is how long doesit take from you to get the
sample from the tumor to makingthe actual mRNA vaccine for
them?
How long does that process take?
SPEAKER_01 (29:31):
That's a great question.
And that's actually reallyimportant for our trials because
uh I didn't fully get into kindof how long that takes and what
we do while we're making thetreatment.
Um, but so it takes aboutsix-ish weeks from when we take
the tumor out of the patient uhto making the um the lipid
(29:53):
nanoparticle.
Um and so that gives likethere's a gap there of about six
weeks where you have a patientwho still has cancer and needs
to be treated.
Um and so for some of ourclinical trials, if it's a newly
diagnosed patient, what we'reable to do is we're able to give
them the kind of normalradiation treatment that um we
(30:14):
uh we might uh be giving asstandard of care.
Um and so that gives a goodlittle bridge to get to the
patient's personalized lipidnanoparticle.
For patients where we'retreating them when the cancer
has come back or it's recurred,um what we do there is we
actually do use an off-the-shelfum, you know, lipid nanoparticle
(30:37):
because we think that using thisnon-specific um uh peptide uh
based lipid nanoparticle, whileit may not be specific for that
patient's cancer, we have shownin uh some of our preclinical
testing that it can actuallystart the process of priming the
immune system.
We're starting to reprogram umthe immune system so that way
(31:02):
when we give the personalizedtreatment, it may respond even
better than a a patient thatdidn't get that those priming
doses.
SPEAKER_03 (31:10):
So at least help it it helps bridge that gap, like
you were saying, at least forthose six weeks where you're
kind of waiting.
SPEAKER_01 (31:15):
Exactly.
That's the that's the hypothesisum or you know, kind of our our
thought process right now.
Um I think um, you know, we'llkind of have to you know see how
that goes.
SPEAKER_04 (31:26):
Right.
Wow.
Interesting.
Is there um this just kind ofstimulated a question for me?
Uh is there a length oftreatment for the for the um uh
mRNA?
SPEAKER_01 (31:39):
That's another great question that we're trying to
answer.
Okay.
Um so at least like right now,you know, we're uh we're
thinking like, you know, let'stry giving it over a whole year.
Okay.
Um because we we don't reallyknow like um after we give the
lipid nanoparticle, how long isthe immunity that you induce
(32:00):
against the patient's tumorgonna last?
Is it gonna stick around for sixmonths?
Is it gonna stick around for onemonth?
Is it gonna stick around for 24hours?
You know, I I'm not entirelysure.
And yeah, like to your pointearlier, the the other question
is like, do you get kind of anamplification of the um immune
response with more treatmentsthat you give?
(32:21):
If you give three nanoparticles,is that enough to teach the body
to permanently recognize uh thecancer?
Do you need to give it for awhole year to give it durable
immunity or to at least um keepthe immune system activated long
enough to wipe up any lastremaining tumor cells that are
(32:42):
there?
We're not sure.
We know that we can make um youknow enough of the lipid
nanoparticles to last for awhole year.
Um whether they need to get itfor that long, or if we can you
know kind of cut it off afteryou know three or five or
whatever arbitrary number ofdoses, um, I think that's an
open question as well.
SPEAKER_03 (33:03):
Okay, interesting.
So still things to learnobviously there's still things
to learn.
Okay.
Yes.
Wow.
SPEAKER_04 (33:08):
Wow, yep.
So, Dr.
Ligan, thank you so much uh foryour work and for kind of taking
your time to come and talk withus today to explain all of this.
This has been fascinating.
Um this trial represents anexciting new chapter, obviously,
in pediatric cancer and the carefor those kiddos and their
families.
(33:28):
And we obviously will bewatching and cheering for you
guys very much as the rest ofthis unfolds.
Um, do you have any parting, anyparting words you want to share
with us?
SPEAKER_01 (33:40):
Yeah, just again, I'm I'm so thankful for the
collaboration, you know, withthe the PICU.
Uh, you know, we wouldn't, youknow, feel as confident as we do
about moving this treatmentforward if we didn't know that
you guys were watching over ourpatients with a you know very
watchful eye and ready tointervene with any um toxicity.
(34:00):
And um I think that really onlyby having a great team that is
fully invested can we move newtreatments forward like this
safely and really answer theimportant questions that we're
all asking.
Excellent.
SPEAKER_03 (34:16):
Wow.
Well, thanks everyone forjoining us in the Gator Picky
podcast.
And we will see you next time.
Thank you, Dr.
Ligan.
We really appreciate it.
SPEAKER_04 (34:24):
It's been wonderful.
Yes.
SPEAKER_01 (34:26):
Thank you guys very much.
At least I managed to set up.
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