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Cancer Immunotherapy: 2020 Research Update and a Look Ahead with Dr. Padmanee Sharma

Cancer Immunotherapy: 2020 Research Update and a Look Ahead with Dr. Padmanee Sharma

welcome to the Cancer Research Institute Cancer Immunotherapy
and New Patient Webinar Series. Today is Wednesday,
January 8, 2020. And the title of today’s
webinar is Cancer Immunotherapy: 2020 Research Update
and A Look Ahead. Before we begin, I’d like to
thank our generous sponsors who have made this webinar
series possible– Bristol-Myers Squibb,
with additional support from Foundation Medicine. My name is Arthur Brodsky and
I’m the senior science writer at the Cancer
Research Institute, a nonprofit organization
established 67 years ago, with a mission to save more
lives by funding research that aims to harness the
immune system’s power to conquer all cancers. This work has contributed
to the development of lifesaving immunotherapies
for a variety of cancer types. We present this webinar series
to patients and caregivers to help them understand
what immunotherapy is and how it differs
from other treatments, to provide information on the
latest developments in research and treatment, and
to connect patients to immunotherapy
clinical trials. Now it is my pleasure to
introduce today’s expert speaker. Dr. Padmanee Sharma
is a professor in the departments of
Genitourinary Medical Oncology and Immunology, as
well as the scientific director for the immunotherapy platform
at the University of Texas MD Anderson Cancer Center, and also
the co-director of the Parker Institute for
Cancer immunotherapy at MD Anderson Cancer Center. Dr. Sharma is a trained medical
oncologist and immunologist whose research work is focused
on investigating mechanisms and pathways within
the immune system that are responsible
for tumor rejection and clinical responses. She is the principal
investigator of multiple immunotherapy
clinical trials and conducts translational
laboratory studies related to these trials which enable her
to develop novel immunotherapy strategies for the treatment
of cancer patients. Dr. Sharma received the Emil
Frei III award for excellence in translational
research in 2016 and was inducted into
the American Society for Clinical
Investigation in 2018. She is the recipient of
the 2018 William B. Coley award for distinguished
research in tumor immunology, CRI’s highest scientific honor,
and a member of both the CRI Scientific Advisory Council and
the CRI Clinical Accelerator clinical and scientific
advisory committees. So thank you for joining
us today, Dr. Sharma. PADMANEE SHARMA: My pleasure. Thank you for having me. ARTHUR N. BRODSKY: So 2019
capped an incredible decade for immunotherapy. And before we look
at the upcoming year, I was hoping you
could kind of quickly recap some of the most
important advances and approvals from this past year. PADMANEE SHARMA: I think in
2019, we made a lot of advances with immunotherapy and
focusing specifically on immune checkpoint therapy. I want to point
out that we’ve had previous approvals,
for example, in tumors like melanoma and lung cancer. And I think in the past
year, we saw an approval in breast cancer
for the first time. And that’s exciting
because for many people that we’re treating
breast cancer, the prior clinical
trials in immunotherapy did not work as well. And for the most
part, breast cancer is what we consider
a cold tumor. And so to see that we could
get treatment for breast cancer with clinical efficacy and
clinical responses that led to FDA approval
for a combination with an anti-PD-L1 agent plus
chemotherapy for this tumor type was very reassuring. We still have a
lot of work to do to get even more patients to
respond in terms of breast cancer treatment, but
I think we’re starting to see now that it is possible. And 2019 was the year for that. I think 2019 was also the year
for another difficult tumor type which is
pancreatic cancer, where we were able to see results
at another combination trial, where we included
an anti-PD-1 antibody with an anti-CD40 antibody
and chemotherapy again in this novel
triplet combination. And we’re able to see
clinical responses for the first time in patients
with pancreatic cancer as a result of these
kinds of immunotherapies. So I think we have new
approvals and new advances that we can build upon for 2020. ARTHUR N. BRODSKY:
That’s great to hear. And I’m really glad
you mentioned– you brought up breast
cancer and pancreatic cancer specifically, which
as you mentioned, have been really hard
to treat in the past. And hopefully,
especially with respect to that pancreatic
cancer one, while there haven’t been that many
patients treated so far, hopefully, it will
continue to be effective as more patients are treated. So in that same
vein, what might we be able to expect in terms
of potential progress against some other hard-to-treat
types of cancer in the coming year? PADMANEE SHARMA: Yes, I think
outside of the breast cancer and pancreatic
cancer space, we’re also dealing with prostate
cancer and glioblastoma multiforme, for example,
as other tumor types that have not had approval with
immune checkpoint therapy agents. And so these are still
difficult to treat tumors that we’re working with. In prostate cancer,
we’re beginning to see again that it will
take combination strategies. And there were
data presented with an anti-PD-1 and
anti-CTLA-4 that looked promising in prostate cancer. And hopefully, as
we see more data from larger numbers
of patients, we’ll be able to figure
out whether or not that’s a combination
that can be moved forward for approval, hopefully, if
we can see the data again in these larger trials, as well
as the new PORTER trial, which is this clinical study
where we’re looking at an adaptive model as
we take multiple agents in the combination for
treatment of prostate cancer. So in this PORTER
study, we’ll look at multiple different
combination arms to see which combination
can potentially be beneficial for patients
with prostate cancer. So again, I think in the
hard-to-treat cancers, such as breast, pancreatic,
prostate, and glioblastoma, I’m hoping that 2020 will
show new data that we can now look forward to
possible approval of immunotherapy agents in
these tumor types as well. In the setting of
glioblastoma, there have been new data to indicate
that myeloid cells are an important component. And although we’ve
been targeting a lot of T cells with the immune
checkpoint therapy agents, such as anti-CTLA-4 and
anti-PD-1, I think in 2020, we’ll start to see
targeting of myeloid cells as well as a
combination strategy with the previous anti-CTLA-4
and anti-PD-1 agents to hopefully get clinical
responses in tumor types like glioblastoma. ARTHUR N. BRODSKY: We
share that hope as well. And just real quick, I
was wondering if maybe you could elaborate a little bit
on what the myeloid cells are. Obviously, I think T cells kind
of get most of the attention. And sometimes, it
might be easy to forget that there are other
cells in the tumors such as the myeloid cells
that can really dramatically influence outcomes. PADMANEE SHARMA: Absolutely. I mean, T cells, of
course, are the soldiers. So T cells go out to do the
job of attacking and killing the tumor cells. But the T cell response is
dependent on other cells within the immune system,
such as dendritic cells and myeloid cells. And if myeloid cells
give out signals to the T cells that make
the T cells stop working, or make the T cells not
capable of becoming activated, then those T cells will
never be able to do their job against the tumor cells. So we have to study the
myeloid cells, for example, to understand what signals they
are propagating to the T cells within the tumor
microenvironment, and how can we manipulate those
signals from the myeloid cells so that they are giving the
T cells the right signals for the T cells to go out and
be soldiers against those tumor cells? ARTHUR N. BRODSKY: Yeah,
I think it’s definitely a very exciting space. And hopefully, as your studies
and other people’s studies start to improve
our understanding of the relationship and how all
these different cells interact, hopefully, it’ll lead
to the development of better strategies for
patients in more cancer types. And so while it’s
kind of become clear that immunotherapy by itself,
it did help against some tumor types, specifically,
the melanoma, bladder cancer, lung cancer,
and a few other types, immunotherapy has worked
when it’s used alone. But we’re now really
starting to appreciate that the immune system’s
power against cancer can be enhanced by combining
different types of treatments, as you mentioned, in the
pancreatic and prostate cancer trials. And nowadays, we also have novel
approaches like CAR-T cells and vaccines that can provide
clinicians with new tools to treat patients. So what are your hopes for
these cutting-edge strategies in the coming year? PADMANEE SHARMA: I think
these strategies are going to be, again, moving forward. Especially in the
CAR-T cell space where we’ve seen dramatic
clinical responses and FDA approvals of some
CAR-T cell therapies, we’re going to now be able
to hopefully take that into other tumor types
beyond liquid tumors that we’ve been treating,
or the hematologic malignancies that
we’ve been treating, and hopefully even
start thinking about treating
solid tumors maybe with the potential for improving
survival of these CAR-T cells by genetic manipulation. And I know, for
example, there are studies using CAR-T
cells where the PD-1 has been deleted from the T cells. And maybe this will lead
to data that maybe we can combine immune checkpoint
therapy and CAR-T cells, even. So those are some of
the exciting studies with CAR-T cells. I think in terms of
vaccines, they’ve gotten a bad rap in the past
because vaccines, by themselves with monotherapy,
have not worked well in clinical trials with
very few exceptions. And sipuleucel-T, for
example, is one of those. But they’ve still
not really lived up to the promise of what
immunotherapy can do. And that’s because I
think vaccines are also going to require
combination strategies with immune checkpoint
therapy agents. And that will then lead to more
effective anti-tumor responses. So I have a lot of hope
for seeing vaccines combined with immune checkpoint
therapy in the future. ARTHUR N. BRODSKY: Great. And like you mentioned,
I think by themselves, they haven’t– the vaccines
haven’t provided maybe the strong responses
that we’d hoped, although on a cellular level,
I think from my understanding, a lot of the sites have
shown that the vaccines are succeeding and at least
starting these immune responses. But there’s other things,
such as checkpoints, that maybe hold them back
from accomplishing the goal of eliminating the tumor. Is that correct, that maybe
the vaccines are maybe just the first step in
a combination strategy that then they need to be
combined with something else to kind of unleash them? PADMANEE SHARMA: Yes, certainly. I think vaccines
are one component. But they allow for initiating
that immune response, but they may not
allow for maintaining the immune response, since
the immune response is well-controlled,
as you mentioned, by multiple check points. And so that’s why combination
strategy will be important. I think it will
also be important for us to redefine what
we think of as vaccines, because many times,
we thought of vaccines as tumor antigens
that were shared among many different patients. And more and more
people are beginning to recognize the importance
of these neoantigens which seem to be specific for
each patient’s tumor. And are those going to
be the best vaccines to use as compared to the
shared tumor antigen vaccines? And these are things–
these are questions that we’ll have to address in
the future in terms of research and clinical trial development. ARTHUR N. BRODSKY:
And so I want to focus real quick, you mentioned
the neoantigens, which are– every patient’s tumor
is somewhat different, because aside from
genetic twins, everyone starts out with
their own unique genome. But as tumors evolve,
the mutations that occur are, in some ways,
random in every patient. No patient– no two patients
have the same exact types of mutations in their tumors. But one of the other
kind of concerns that’s out there, especially
on a lot of patients’ minds, is the cost of immunotherapies,
especially with the kind of, I guess, more
towards with the cell treatments but some
others as well. And some people might
be thinking, you know, if we have to make a
vaccine for each patient because each patient’s
tumor is different, that might get really expensive. Is that necessarily the
case with the vaccines that are being used today? PADMANEE SHARMA: No. Actually, it turns
out, the vaccines are quite easy to make. Synthetic peptides or proteins
are quite easy to make and should be
considered very cheap. And I think in a lot
of ways, you know, even as we make
monoclonal antibodies, it’s pretty cheap to make them. It’s just, how will they
be priced by companies is a different question
and something that I think we need to bring a lot of
different people to the table, including scientists and
physicians and pharma companies and regulatory
groups, to try and make those decisions together. But from our standpoint, we
see that making the vaccines is actually not an
expensive process. ARTHUR N. BRODSKY:
That’s good to hear. And by that same token
as far as bringing all the different
stakeholders to the table, you’ve had some experience
working with our CRI Clinical Accelerator, of trying to
not necessarily focusing on the prices of these
things, but at least getting all these people in the
same room and trying to, you know what? We’re all going
after the same goal of trying to eliminate cancer. And doing it in
these different silos might not be the
most productive way. So could you talk
a little about kind of these efforts on the
collaboration front, about how these might help
lead to better strategies? PADMANEE SHARMA:
Yeah, I mean, it’s been clear that
the more people you put in the room that are
focusing on a problem, the better the chances
are that you can come up with strategies that work. You know, we each
have our strengths that we bring to the table. And not one person is going
to solve all the problems. So that’s why it’s important to
have teams that work together. And I think that was a
problem, and maybe still is a problem to a certain extent. Because the language
that we all use and the ways in which
we think of the problem, we need to be able
to communicate our science in a way that
somebody else can understand. So sometimes, the
regulatory teams may use a different
set of jargon and the scientists may use
a different set of jargon. And when they
communicate, they’re not understanding
each other because it sounds like two different
foreign languages, right? So we’re trying now to be better
at breaking down our jargon and our scientific
concepts into lay terms that anyone can understand. And that, I think that
level of communication will help the process
as we each start to see the strengths that
we can bring together to really formulate effective
plans for how to make things work better, a
combination of strategies, how to have multiple
different pharma companies be able to combine their different
agents in clinical trials, and how to hopefully
bring drug prices down. ARTHUR N. BRODSKY:
I definitely agree that that is an important
component that will hopefully help move the
entire field alone. So at this point, I want to
move to another promising area of research that’s kind
of a buzzword these days, and that’s biomarkers. These can take many
different forms. But in general, these
are kind of pieces of information about a patient
or their general health or their tumors or their
immune system’s health that can kind of help doctors
better understand the individual patient’s disease
and potentially even help guide the doctors with respect
to which treatments might work best for individual patients. So could you talk a little
bit about biomarkers and what you’re excited
about with respect to 2020, and what more we might
learn about them? PADMANEE SHARMA: Yeah, I think
biomarkers are so important because they really help
us to select patients according to their tumors
and what treatments may work best for them. And I think this all came about
in the era of genomic medicine when we were really
basing our treatment strategies on the specific
mutations within the patient’s tumor. So for example, if a
patient had a BRAF mutation, then the patient
got the drug that targeted the BRAF mutation. And the drug was
developed specifically for targeting the BRAF mutation. So it made a lot of sense
to use the BRAF mutation as the biomarker to select the
patients and that type of tumor for the BRAF
inhibitor, for example. So I think that worked
out well in that era of genomic medicine. And it’s been
something that we’ve been struggling a bit with
in the immunotherapy world because the immune
response is so dynamic. It changes day to day. As we’re sitting
here and talking, our immune response is changing. So to say that we can
have a single biomarker at a single time point for
patients to select a treatment may not be possible. And we’ve had to start thinking
a little bit broader than that. And what we need
to do, maybe, is think about how to use an
immune-type related biomarker as well as the
genomic biomarkers so that we’re looking at
multiple different components to then select
patients for treatment. And so I’m really hoping that we
bring together multiple fields. So genomic medicine
fields will look at mutation status and
the immunotherapy field and the immune experts
within the fields will look at what the
immune biomarkers would be that can combine
with genomic biomarkers. So those are some
ways to think about it and I think that those the kinds
of advances we’ll see in 2020. Because the immune
response is so dynamic, It’s not going to be a single
biomarker in a single time point, the way we were
lucky to have that happen in the genomic field. I also think that
the new methods, such as liquid biopsies and
novel imaging strategies, will be helpful in looking
at multiple biomarkers and combinatorial biomarkers
for patient selection. So again, this
idea of combination comes into play, as we’re
discussing combination therapies, and now we’re talking
about combination biomarkers that will help with
the patient selection. And breaking down silos between
genomic medicine and immunology will also be another
piece that we see happening in 2020 to then
move the field forward and help us with the patient
selection for treatment. ARTHUR N. BRODSKY: Definitely. And so I do want to hone in, you
mentioned the liquid biopsies. Just to pull back for a minute,
traditionally, the best way doctors have had to learn
about a patient’s cancer is to get a biopsy and get a
physical piece of their tumor and then study that in the lab. But this has some
drawbacks, obviously. First and foremost, it’s
uncomfortable for the patient to have them keep
coming in, like you mentioned, to get these
sequential samples. And secondly, it’s not always
possible for various reasons. So going back to the liquid
biopsies, which I just want to clarify for our
audience, would be– or at least, one of
the major forms of it would be taking a
sample blood draw and then using that to analyze. How could these be
beneficial both for patients and for physicians? PADMANEE SHARMA: Yeah, I
think the liquid biopsies are promising. I think they still have
to be proven, of course. And that’s why we’re
doing research on them. But I think it will be
very helpful for patients because it is a
simple blood draw. It’s not as invasive as
having to go under a CAT scan with a needle to take
a biopsy of a tumor, for example, that
may be embedded in their abdomen
or deeper tissues. So I think the liquid
biopsies can be very helpful from that standpoint. And then the liquid
biopsies, as you mentioned, will be easier for physicians
and researchers too. Because if you need to
get multiple time points because a single
time point is not going to be able to
give you the answers and you need to see the dynamic
changes in an immune response for example, then
the liquid biopsies are much simpler
because you can do that multiple times to get
those samples to do the research work. So I think from that
standpoint, liquid biopsies hold a lot of promise. But we have to do the
work to really show that the liquid biopsies can
give the same amount or as meaningful and relevant
the information that we get from the actual
biopsies of the tumors. And that’s the research
we’ll see happening in 2020. ARTHUR N. BRODSKY:
That’s great to hear. So now I want to
move from biomarkers to another buzzword that’s
been in the news a lot, especially this past year, and
that’s the microbiome, which is the collection of the
trillions of bacteria and other microscopic organisms
that reside within us– a lot of them in our
gut tract, but also on our skin and the lungs
and some other areas. So what do you think 2020
might have in store for us when it comes to better
understanding and taking advantage of that
complex relationship between the microbiome, our
immune system, and cancers and how we might be able
to use that to improve care for patients? PADMANEE SHARMA: Yeah, I
think the data is definitive. And the evidence is
great to indicate that the microbiome is
playing a role in how the immune response develops and
how the immune response that’s generated by things
such as immunotherapy with immune checkpoint
agents evolve for leading to anti-tumor
responses and clinical benefit. So the microbiome is definitely
playing an important role, it’s just now understanding
which microbiome that is. So we need a really
deeper understanding of the types of
microorganisms that we’re talking about and
then whether or not we can manipulate the microbiome. And how do we do that? Do we give that– do we do that in terms of
giving patients microbiome? Do we take microbiome from
patients who have the good ones and transfer them to patients
who don’t have the good ones? Are there ways to
give other therapies to manipulate the microbiome? Do we avoid things like
antibiotics in certain settings so that we don’t eliminate
the good microbiome? And then there are
nutritional factors. Do we give patients
certain high fiber diets, for example, that can help
drive certain microbiomes? These questions are
still unresolved. But I think they’re all being
addressed in different research formats, whether it’s a
clinical trial or more laboratory-based studies to look
at the types of microorganisms that we’re talking about. And with the data that’s being
generated from these studies, I think, we’ll have
a sharper focus of how we can really
manipulate the microbiome and specific microorganisms
within the microbiome to drive the clinical
benefit that we’re seeing with immunotherapy agents. ARTHUR N. BRODSKY: Yeah,
I think you brought up a lot of great points there. You know, it’s great that
we’ve come to appreciate its potential impact. But at the same time, it’s
such a complex situation. There’s so many different
types of bacteria, so many different
potential interactions. And it’ll really be
important, as you mentioned, to kind of tease apart
what are the causes and effects in that situation. And so now, a little
bit before we wrap-up, obviously, it’s going to
take us longer than just 2020 to achieve our ultimate goal,
which is to ultimately cure all cancers. To that end, in
your opinion, what are the biggest
questions and challenges in the field that you hope
we’ll start to make progress on in 2020 in order
to create a even better future for patients? PADMANEE SHARMA: I
think 2020 is going to be seeing even
more work in how we study the immune response. You know, I’ve
been an oncologist for a really long
time, 20 plus years. And in oncology, we’ve always
looked to laboratory data to help drive what we’re
going to do in the clinic. And so the laboratory
data, though, came from mouse models that
didn’t have an immune system. Can you believe that? We studied a lot
of tumor responses in these sort of
xenograph models, or mice that lacked an
immune response because we wanted to look at how the drugs
targeted the actual tumors. And without taking the immune
response into consideration, we were missing a piece
of the picture, clearly. So I think in 2020,
we’re going to start to look at how do we
develop better laboratory models to study the immune
response and the tumor microenvironment, and
drugs within the tumor microenvironment a
little bit better? That’s one. But two, I think importantly,
we’re going to recognize that actually, the immune response
in patients, that needs to be studied even better. And we need to do a
better job of what I term reverse translation. So for many years,
translation consisted of looking at what
happened in mice and then taking
it to the clinic. Now I’m hoping, because
we have over 2,000 plus immunotherapy trials ongoing– so we have a lot of patients
receiving immunotherapy– that we can then
take the samples from the patient,
the tumor biopsies and the liquid biopsies
and the blood samples, to take those
samples and take them back to the lab to study the
patient’s immune response and the patient’s tumors,
so that we can design, then, proper
scientific laboratory studies based on patient data. And generate the models and
generate the mouse models specifically from
the patient’s data to test specific hypotheses
that we can then figure out, what are the appropriate
combinations to overcome some of the resistance? And to help more patients
and bring that back into the clinic. So these types of reverse
translational studies I’m hoping will be a
bigger part of 2020. We’ve already seen some of
the data coming out from that. So addressing this challenge of
how do we blend and integrate the laboratory
with the clinic, I think we’ll see
progress on that front. But we’re not missing
the vital components like we did before
when we were just studying mouse
models with tumors but without an immune system. ARTHUR N. BRODSKY: Yeah, I think
that’s so crucial, like you mentioned, that we’re at
the very least starting to, as you mentioned, the mice
without immune systems. And being able incorporate that,
whether it’s the microbiome, all these different things. And as you mentioned,
it’s not just a one way route from the mouse
and then try it in humans. And if it doesn’t work, go
back to the drawing board. It’s this continuous cycle
where what we do in the lab informs what you
do in the clinic, and then what we observe
in the clinic then informs the next round of
experiments, and so on. I think it’s become
a very good model. And hopefully,
it’ll pay dividends. So that is all the time
that we have for today. Thank you so much, Dr.
Sharma, for your extremely informative and
inspirational responses. For more of our webinars and
the additional resources that we have for patients and caregivers
as part of CRI’s answer to cancer educational programs,
we encourage you to check out our website at Here, you can read
and watch stories shared by others
who have received immunotherapy treatments across
a wide variety of cancer types. You can register for one of our
immunotherapy patient summits, browse our entire library
of past webinars featuring the world’s leading
immunotherapy experts, such as
Dr. Sharma, access information on other
resources, including treatment, emotional support, and
financial assistance, and find help locating an
immunotherapy clinical trial. Finally, I’d like to thank
our sponsors one last time for making this webinar
series possible, Bristol-Myers Squibb with additional support
from Foundation Medicine. I’d also like to
recognize and thank BioRender, whose
platform was used to create the majority of the
graphics that you saw today. And again, you can watch this
and all of our other webinars on our website at to learn more about the
immunotherapy options and a number of cancer types. Dr. Sharma, I just want
to thank you so much again for taking the
time with us today and for the amazing work
that you are doing to advance immunotherapy for patients. We wish you the best of luck. PADMANEE SHARMA:
Thank you so much. Happy 2020 to everyone. ARTHUR N. BRODSKY:
Thank you, Dr. Sharma.

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