Latest / UF Health MedEd Cast / Exploring the Complexity of Cancer: How mRNA Vaccines Could Change Everything

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Exploring the Complexity of Cancer: How mRNA Vaccines Could Change Everything · UF Health MedEd Cast

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  Melanie (Host): Welcome to UF Health Med EdCast with UF Health Shan's Hospital.
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  I'm Melanie Cole, and today we are highlighting groundbreaking therapeutic
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  mRNA cancer vaccine research.
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  Joining me to discuss this exciting research is Dr.
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  Elias Sayer.
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  He's a pediatric hematologist-oncologist and a professor in the Department
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  of Neurosurgery at the University of Florida College of Medicine.
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  He's also a stop children's cancer, Bonnie r Freeman, professor of pediatric
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  oncology research in the UF departments of neurosurgery and pediatrics.
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  Dr.
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  Seor, thank you so much for joining us to discuss this very exciting topic.
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  as we get into this, I'd like you to explain a little bit about the
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  complexity of cancer, the ecosystem.
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  How is the field of mRNA cancer vaccines advancing the concept
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  of personalized cancer therapy?
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  Elias Sayour, MD: Yeah.
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  Thank you for having me.
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  Melanie, certainly.
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  Cancer is, very complex and, that complexity, is one of the real
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  grand challenges to cancer vaccines.
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  Cancer is not just, a bunch of cells that, divide, indiscriminately.
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  So a lot of people think of cancer as just exponential growth, 2 4 8, 16 32.
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  but in truth, cancer, is more than that.
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  tumors divide like that, but benign tumor is not the same as cancer.
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  Cancer is defined by its ability to invade, destroy tissue.
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  And also, cancer is not just cells.
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  It's an environment.
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  It's an entire ecosystem.
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  In this ecosystem, cancer has its own blood vessels.
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  Cancer has its own metabolism.
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  Cancer has its own immune system in many contexts.
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  An immune system that doesn't fight the cancer or see it as foreign, an
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  immune system that sees the cancer as self or a wound, that it has to heal.
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  That healing environment that a clumsy immune response is creating,
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  actually facilitates the cancer growth.
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  And so you have chronic inflammation in these tumors that
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  facilitates the tumor growth.
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  Everything I mentioned is a part of an ecosystem.
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  That is extraordinarily challenging for a cancer vaccine to work.
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  Even if a vaccine elicits an immune response, that immune response often
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  cannot penetrate this environment, survive in an environment like this,
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  and even if it could, the cancer as it's doing, all of this continues to evolve.
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  Evolves away from the immune system.
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  And these are significant challenges for a cancer vaccine.
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  And in my mind, one of the major reasons why, vaccines haven't worked,
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  for a really, really long time.
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  But it's also my hope that mRNA will overcome these obstacles.
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  Melanie (Host): Dr.
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  Seor, you've described this work as both deeply scientific and deeply personal.
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  Tell us a little bit about the moment when this approach to the mRNA Cancer
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  vaccines first felt possible, and why did you believe this platform could achieve
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  this, that prior efforts really could not.
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  What did you see in those early models that told you that this wasn't
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  just another incremental advance?
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  Elias Sayour, MD: Yeah, a great question.
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  So mRNA, we've been studying mRNA for, 10, 15 years now.
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  our group and really we've made some pretty remarkable
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  discoveries, in that time that.
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  Really have allowed us to believe this can be the solution, to getting
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  cancer vaccines, or I should say therapeutic cancer vaccines to work.
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  And when I say therapeutic cancer vaccines, I mean treatment
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  vaccines, treating something after it's already started.
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  And one of those things that we discovered was.
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  mRNA could reprogram these ecosystems.
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  mRNA can create an environment even in the cancer with a single dose that could
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  reprogram the tumor microenvironment from a, chronic inflammatory response that
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  facilitates the tumor growth to a response that actually starts fighting the cancer.
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  And the fact that this could happen as rapidly as we observed, within
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  24 hours of PEth dogs with brain cancer, as an example, within 24 hours
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  of a single dose that we could see in these tumors, the immune system
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  starting to wake up against cancer.
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  That was very heartening for us.
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  so much so that it created this idea of using mRNA as a universal tool.
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  We discovered this reprogramming, this rapid reprogramming could
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  happen with nonspecific mRNA vaccines, meaning of an mRNA that
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  wasn't even specific to the tumor.
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  And that idea of a universal cancer vaccine is something that I think can now
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  be created and engineered through mRNA.
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  But number two, we found that personalized vaccines, if the
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  mRNA is specific to the cancer.
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  It works even better.
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  And the beauty of mRNA, unlike a lot of cancer vaccine platforms, is it can adapt.
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  You can update the vaccine.
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  To be, more and more relevant to the cancer.
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  Meaning you make a vaccine when you first biopsy a tumor, but then you
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  can make updated vaccines if that tumor were to recur or come back.
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  Meaning your vaccines can evolve as the cancer is evolving, And in
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  that way you can now provide almost an updated vaccines that outcompete
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  the evolution of the cancer.
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  And so that's something that can happen really through the groundbreaking
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  power of mRNA, that you can, build these to target as many things as you
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  want and update them in a way that can be done through a single approach.
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  Melanie (Host): That's absolutely fascinating and really, really exciting.
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  And Dr.
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  Sayer, so this exciting observation you were just discussing that even a vaccine
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  not specific to any particular tumor or virus, as long as it's mRNA vaccine,
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  could lead to tumor specific effects.
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  What patient populations or tumor types characteristics appear most promising
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  for this approach at this stage?
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  Elias Sayour, MD: this idea of a universal cancer vaccine really
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  started in our lab, this discovery that again, something completely irrelevant
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  to the tumor, could wake it up.
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  And could sensitize response to other immunotherapies, like
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  immune checkpoint inhibitors.
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  we saw that in, mouse models of melanoma.
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  This was before the pandemic.
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  Now the pandemic allowed us to ask a really interesting
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  question, And that question is.
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  If a non-specific mRNA vaccine can wake up the immune system and sensitize response
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  to checkpoint inhibitors, what happens to melanoma patient's and non-small cell
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  lung cancer patient's who are receiving another non-specific mRNA vaccine?
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  This being the sars CV two, the CVID 19 mRNA vaccines within a hundred days of
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  also receiving conventional immunotherapy with immune checkpoint inhibitors.
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  And looking backwards, which is an important distinction.
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  We're looking backwards in these studies.
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  These are retrospective studies that have to be validated in prospective
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  studies, forward-looking studies.
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  But looking backwards, we found a near doubling in survival outcome of
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  patient's receiving the COVID-19 vaccine.
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  Receiving conventional immunotherapy of immune checkpoint inhibitors within
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  a hundred days of those vaccines.
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  And you're doubling in survival for patient's with skin cancer, melanoma and
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  lung cancer, non-small cell lung cancer.
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  So, we've gone back and even shown that the COVID vaccine works in
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  our mouse models to sensitize response to checkpoint inhibitors.
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  This all basically tells us that perhaps we already have a universal
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  cancer vaccine in our midst.
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  That can improve response.
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  This being the COVID-19 mRNA vaccine.
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  Now it's worth mentioning the COVID-19 vaccine was not
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  designed specifically for cancer.
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  And even if that were to not work in forward-looking trials, we still
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  believe we can make a universal vaccine that works much better.
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  In waking up the immune response and sensitizing response to checkpoint
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  inhibitors, one vaccine, one master vaccine for all patient's.
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  But if indeed, these forward looking trials actually look promising, meaning
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  the COVID-19 vaccine works to awaken the immune response, You know, we think
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  that could really transform the field.
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  Melanie (Host): Wow, that's unbelievable.
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  Now, immune activation along those lines raises safety concerns
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  What's reassured you most about the tolerability of this approach?
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  Elias Sayour, MD: I think that's really the most exciting thing
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  about the COVID-19 mRNA vaccine.
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  I mean, this has been, deployed, hundreds of millions of times, over
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  and over again, and really that safety profile that we have from so many
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  patient's who've been dosed with this, that gives us some confidence in this
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  approach, as a, what we believe would be a very safe way of activating the
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  immune response in a universal manner.
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  At the same time, we have to run the trials to really get a really
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  good indication of comprehensive safety in conjunction with these
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  immune checkpoint inhibitors.
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  That's why those trials are important to run, but we're certainly heartened
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  by the safety data, in trials that have been conducted to date
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  for, infectious COVID prevention.
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  Now if that vaccine doesn't work and needs to be engineered to
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  be even stronger, for cancer.
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  we think that's an approach that could work, but then also when you're activating
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  the immune response in an even stronger manner, there are more side effects
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  that people might be at-risk for.
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  And, uh, Those are things that we're very cautious about.
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  That's why we have to run these forward looking trials and, make
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  sure that these things are safe.
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  and why we're heartened that the COVID vaccine could be an answer because of
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  its safety profile, but ultimately.
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  We have to run these trials to know for certain.
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  Melanie (Host): So from a clinician standpoint, Dr.
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  Sayer, how complex is it to deliver this therapy compared with
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  other advanced immunotherapies?
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  How does the delivery system of specifically mRNA vaccines
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  influence their efficacy and safety in this type of cancer therapy?
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  Elias Sayour, MD: Yeah.
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  Great question.
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  Right now, the COVID vaccine we know is, intramuscular.
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  again, if that works, that's.
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  We think that could be a, safe, opportunity to non-specifically
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  activate the immune response to awaken it, for response to immunotherapy.
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  but if it doesn't work, we think there are ways of making it stronger.
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  One way to do That is to maybe give an intravenous vaccine, and maybe a
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  vaccine that's designed to elicit an even stronger non-specific immune response.
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  We've certainly made our own vaccines here at the University of Florida.
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  an onion like design of mRNA, aggregates that we inject right into the bloodstream
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  that, can be very, very powerful, in activating the immune response.
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  The dog studies I mentioned earlier were.
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  Was that vaccine, again, a non-specific vaccine that can reprogram the
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  brain tumors in less than 24 hours.
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  But when you do that, There are also more side effects.
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  There are, risks of cytokine response syndrome.
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  That's where you activate a lot of signals of the immune response.
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  That can cause fever, cause muscle pain, can it cause drops in blood
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  pressure, even cause increases in oxygen requirements in some patient's.
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  So Those are all.
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  potential concerns and why?
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  If we, started using more aggressive approaches in activating
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  the immune response, we think those could work even better.
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  But because of these side effects, these have to be really done
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  in very controlled studies.
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  Melanie (Host): So as this work and we're looking retroactive Lee, as
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  you say to those studies and as this work emphasizes personalization, Dr.
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  Sayer, how challenging is it, do you think, practically to design
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  patient specific mRNA vaccines at this scale that we're looking forward to?
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  Elias Sayour, MD: Yeah, another great question.
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  Anytime you personalize something, there is increased cost.
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  There is increased complexity.
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  Most importantly, increased time, time being the most valuable
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  resource that patient's have.
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  And so if it's taking an extra two to six weeks to make a personalized vaccine,
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  that's time that the cancer has to grow.
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  That's also why I believe so much in giving something universally at
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  first, waking up the immune response as rapidly as possible, which can
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  buy time for that personalization.
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  But as you've stated, yes, it, does take time.
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  It takes us here at the University of Florida about six weeks right
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  now to make personalized vaccines.
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  But I will tell you that I think that timeline is going to shrink.
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  I do see an era where we can make personalized vaccines almost instantly.
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  I see the future of mRNA akin to that of a keyboard by the patient's
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  bedside, where you type in the sequence that you want, And then out the
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  other end of a box comes the vaccine.
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  I do see that future, and mRNA is really in the early phases of being advanced
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  into patient's with all sorts of diseases, not just cancer, but for autoimmunity,
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  for neurodegenerative conditions.
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  As a gene therapy And the ability to customize, a therapy just by changing
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  the sequence, I think we're gonna get much quicker and better at doing that.
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  And as we cut down the time to personalization, I also think we'll cut
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  down the, cost, and some of the complexity around this, hopefully to the point
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  where it may even be a bedside therapy.
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  But right now there is certainly time, associated with making these, so much
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  so that I, do think the universal approach, as a bookend to personalization,
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  is a really important step forward.
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  Melanie (Host): Wow.
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  And it, I mean, as I see it and listen to you possibly even into
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  preventive oncology, and I mean, it is groundbreaking as we say now.
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  One of the things I was thinking about when I was writing these
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  questions is how do you, Dr.
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  Se, or balance the scientific rigor.
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  We're discussing here today, the importance, the technicality of
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  it all, with the urgency that patient's and families feel around
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  these breakthrough therapies.
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  People with melanoma, people with non-small cell lung cancer,
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  people with these cancers where this type of immunotherapy could
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  really be, beneficial save lives.
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  How do you balance that, need it must make you in the lab every day go,
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  okay, we, we have to get this right.
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  Elias Sayour, MD: Yeah.
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  This is a very hard question.
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  Something, uh.
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  I do grapple with every day.
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  we in the lab have to grapple with, the sense of urgency to move this forward
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  as quickly as possible, but also to take the appropriate time that we need to make
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  sure the studies are done rigorously, to make sure that we're putting our
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  best foot forward, to make sure it's done as safe, and as well as possible.
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  it's hard.
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  know, I'm a pediatric oncologist, so seeing children suffering and dying,
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  of diseases that we think that we can, improve through these types of
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  therapies through advancing these trials.
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  I mean, it's hard when those trials aren't there yet.
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  all I can tell you is that it is an incredible motivator as you've
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  mentioned, in helping us, move forward as quickly as possible.
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  but we have to sometimes, go slow to go fast, and I have to remind myself
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  that, that going slow, taking time now means we'll be able to accelerate
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  tomorrow, that we have a responsibility to the patient's of tomorrow, to the
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  people that haven't been diagnosed yet, to make sure that we give them the
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  best chance of having a good outcome.
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  and if we make a mistake now that compromises everything.
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  So, it's hard.
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  Believe me, I, I wanna be in clinical trials for everything and, help
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  especially all these children.
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  but we also have to make sure that this work has legs for, all patient's.
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  And that this technology shows promise for other researchers and
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  other people doing work that really mandates, I think, a strong foundation.
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  So, we're trying to balance that.
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  We certainly don't wanna take any extra time than we need, but I also
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  wanna make sure we take the necessary time to make sure the studies are
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  done correctly And that we answer the most fundamental questions.
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  Melanie (Host): You're a good man and a patient one too.
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  This is such important work you're doing.
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  And finally, Dr.
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  Sayer, as both a physician and a scientist, what advice would you give
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  young clinicians, scientists trying to bridge that gap between bench
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  science and real patient impact?
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  And for trainees and early career physicians listening, what do you feel
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  this work teaches us about the future of physician scientists in oncology?
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  And if you and I were to revisit this conversation in a few years.
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  What do you hope we'll be talking about differently?
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  Elias Sayour, MD: Yeah.
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  What I would tell people it's important to be patient as you described,
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  but also have a willingness to challenge existing paradigms and.
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  When you have a willingness to challenge existing paradigms and to belief, I
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  use this word all the time, belief, belief that it's possible, then I
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  do see that as the groundswell of something great that can be created.
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  But to create something great not only requires, that belief And that vision.
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  But also a willingness to take all of those small steps that
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  are necessary and make sure every one of those steps are correct.
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  And There are times where we don't take the right steps.
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  There are times where maybe we've moved off the right track, but it's important
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  sometimes even to take those steps to learn where the right track is.
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  And that again, that's where patience comes in and understanding that even
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  our failures are teachers for success.
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  Certainly, I think if we try to see, the end of the journey through each
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  and every one of these steps and work as hard as we can to ensure every one
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  of these steps is as rigorous and as well done, then I think we're getting
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  closer and closer to that destination.
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  it's hard, I think, for junior people who, see suffering, especially
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  clinicians who see suffering, which is so significant in the clinic and
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  know how long this journey takes.
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  But I do think that journey is, we have to get that right and it takes time.
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  And it's important to not only be patient, but to believe that we're
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  taking the steps that we need to make the world a better place.
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  And, the only thing I would add to That is community working with other's,
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  other's who challenge us, other's who, bring other layers of innovation to this.
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  That's what creates synergy.
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  Synergy to me is critical.
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  One plus one has to equal one 11 for us to do something
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  extraordinary like cur cancer.
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  But I think the willingness to, believe the willingness to take every one of
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  these steps, the willingness to, to create synergy through collaboration
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  and working with And for other's, all of That is part of the secret ingredients,
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  I would say towards, that greatness that we're all trying to achieve.
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  Melanie (Host): This has probably been one of the most fascinating.
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  Shows that I've done in a very long time.
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  And Dr.
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  Sayer, I can't thank you enough.
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  This is exciting, exciting research, and a very exciting
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  time in your field specifically.
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  And if anybody can do it, you are certainly the man to do it with your
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  team and I thank you so much for joining us and sharing this research,
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  letting us know what's on the horizon because it is a time of advancements and
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  technology and things are moving quickly.
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  And you're right there at the heart of it.
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  So thank you so much.
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  And to learn more about this and other healthcare topics at UF
• 21:05
  Health Chance Hospital, please visit innovation dot uf health.org
• 21:09
  and to listen to more podcasts from our experts, you can
• 21:11
  always visit UF health.org/med
• 21:13
  matters.
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  That concludes today's episode of UF Health Med EdCast with
• 21:18
  UF Health Shans Hospital.
• 21:20
  I'm Melanie Cole.
• 21:20
  Thanks so very much for joining us today.