Immunotherapies for Cancer
May 17, 2021Information
May 16, 2021
Yale Cancer Center
visit: http://www.yalecancercenter.org
email: canceranswers@yale.edu
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- 00:00Support for Yale Cancer Answers
- 00:02comes from AstraZeneca, dedicated
- 00:05to advancing options and providing
- 00:07hope for people living with cancer.
- 00:10More information at astrazeneca-us.com.
- 00:14Welcome to Yale Cancer Answers with
- 00:16your host doctor Anees Chagpar.
- 00:19Yale Cancer Answers features the
- 00:20latest information on cancer care by
- 00:23welcoming oncologists and specialists
- 00:24who are on the forefront of the
- 00:27battle to fight cancer. This week,
- 00:29it's a conversation about immunotherapies
- 00:31for cancer with Doctor Carla Rothlin.
- 00:34Doctor Rothlin is Dorys McConnell Duberg Professor
- 00:35of Immunobiology
- 00:37and professor of Pharmacology
- 00:38at the Yale School of Medicine,
- 00:41where Doctor Chagpar is a
- 00:43professor of surgical oncology.
- 00:45Carla, maybe we can start off by you telling
- 00:48us a little bit about yourself
- 00:51and what you do.
- 00:53I was born in Argentina
- 00:56and it is in Argentina where I did
- 00:59all my initial training in science.
- 01:01I studied biochemistry in pharmacy at the
- 01:04University of Buenos Aires and did
- 01:07my PhD at the University of Buenos Aires.
- 01:10And interestingly,
- 01:11it was in a very different area of research.
- 01:14My PhD was in Neuropharmacology.
- 01:16And then now almost 20 years
- 01:18ago I came to the United States.
- 01:22I came in particular to California
- 01:24to the Salk Institute,
- 01:26where I did my postdoctoral training,
- 01:29and it was there where I became
- 01:32fascinated by immunology and where I
- 01:34started to learn about immunology,
- 01:37and I know today we're going
- 01:39to talk more about it,
- 01:41and after doing my postdoc
- 01:44at the Salk Institute about
- 01:4612 years ago I moved to Yale,
- 01:49where I started my own lab and I'm
- 01:52at the Department of Immunobiology.
- 01:59I've had a wonderful time here and I'm very
- 02:01fortunate to have been able to
- 02:04start my lab at this
- 02:06wonderful University.
- 02:07So tell us more about what your lab does
- 02:11and what you study?
- 02:12We are very interested in
- 02:14understanding the immune response.
- 02:16But in particular,
- 02:17what we're interested in understanding
- 02:20is what are the mechanisms that regulate
- 02:23how much the immune response will be.
- 02:26So how do you regulate the
- 02:28magnitude of the immune response?
- 02:31And also how long that
- 02:33immune response will be?
- 02:35How do you regulate the
- 02:37duration of the immune response?
- 02:39And as you can imagine,
- 02:42understanding the regulation of the
- 02:44magnitude and the duration has
- 02:46tremendous implications every time.
- 02:47They mean responses turn on,
- 02:50so those are the
- 02:53two fundamental features of the
- 02:55immune response that our lab
- 02:57centers around.
- 02:58Right now when we're in the
- 03:00middle of this covid pandemic and
- 03:03people are getting vaccinated,
- 03:05I think a lot of people are thinking
- 03:08about the immune response in terms
- 03:10of vaccines and how long that
- 03:13immunity from the vaccine will last.
- 03:16Has your lab thought about that?
- 03:20How do we gauge how
- 03:23long an immune response will last
- 03:26from a vaccine, for example?
- 03:29That's a very,
- 03:31very interesting question.
- 03:32When you think about the
- 03:36duration of the immune response,
- 03:38you would probably want to also think
- 03:41how the immune system is built.
- 03:44So it turns out that the immune system
- 03:47in mammals, and in humans,
- 03:49has two big divisions.
- 03:53One, which is called innate and we are all
- 03:56born with that type of immune response.
- 03:59And it's the very fast, quick response.
- 04:02And then there's another one which is
- 04:05called adaptive and that is more tailored,
- 04:08more specific to each of the pathogens that,
- 04:11for instance,
- 04:12we can encounter when we're thinking
- 04:15about the duration of the immune
- 04:18response in the context of vaccines.
- 04:20We are thinking that we really
- 04:23want to activate those cells of the
- 04:26adaptive immune system because they
- 04:28have the peculiarity that they can
- 04:31remember, they have memory and that
- 04:33is very important to understand.
- 04:36Our lab has focused primarily on trying
- 04:39to understand what regulates the
- 04:41duration of the more initial immune
- 04:44response of this innate immune response,
- 04:46and the reason why that is
- 04:49also very important is that
- 04:52a response is not so much
- 04:54directed to the pathogen to the
- 04:56microorganism that is infecting us.
- 04:59It can be broader and therefore
- 05:01can potentially have some
- 05:03adverse effects.
- 05:05For instance,
- 05:05inflammation forms part of this
- 05:07very first innate immune response,
- 05:10so we absolutely needed to get the
- 05:12system going to get the immune
- 05:14response going which is absolutely required
- 05:17for inducing this immune response,
- 05:19but it cannot go on forever.
- 05:22So our lab has really focused on
- 05:24trying to understand what dictates
- 05:27the duration of this initial
- 05:29innate immune response.
- 05:31So when
- 05:32you talk about the innate immune response,
- 05:35is that kind of like if somebody got
- 05:39infected with covid, whether they
- 05:41produce a response against that,
- 05:44or is that still more the
- 05:47other longer term response where
- 05:49you develop a memory?
- 05:52It's more the first type of response,
- 05:56so in our system, our
- 05:59immune system, is capable in that it can
- 06:03first recognize general changes.
- 06:05And let's say maybe we are infected just
- 06:09with a bacterial, with a virus, right?
- 06:12And it can detect that and the cells that
- 06:15are involved in detecting that initially
- 06:18are the source of this first response.
- 06:22This innate immune response.
- 06:23That can detect that we've been infected
- 06:26with a bacteria or with a virus.
- 06:29Or with the fungi or parasite.
- 06:32Now, as I was alluding to, there is this other
- 06:36more sophisticated adaptive immune response,
- 06:37and that takes a little bit longer
- 06:40to be triggered, is triggered by
- 06:42first the innate,
- 06:44and has that memory capacity.
- 06:46And what is beautiful also about this
- 06:49adaptive response is that it has the ability
- 06:52to distinguish which bacteria is infected.
- 06:54Or which viruses is infecting us.
- 06:56So just to take the example of a virus.
- 07:00For instance,
- 07:01our adaptive immune response
- 07:02to COVID-19 to SARS CoV2
- 07:04will be different than,
- 07:06for instance influenza.
- 07:08So the adaptive immune response can
- 07:10distinguish that and our lab focused
- 07:12more on the very first response that
- 07:15realizes that you have a virus,
- 07:17but maybe doesn't realize which
- 07:19viruses or realizes that you've
- 07:21been infected by bacteria,
- 07:22but doesn't really realize
- 07:24which type of bacteria.
- 07:26But this first response is fundamental
- 07:29and the very interesting aspect of
- 07:31it is that we are born with it.
- 07:34That's why it's called innate.
- 07:35So as soon as we are born,
- 07:38we are able to react to these
- 07:41microorganisms.
- 07:42And then as we are exposed to them,
- 07:45we are able to induce this
- 07:47adaptive immune response.
- 07:48This learned response,
- 07:50that is the one that then will confer
- 07:53memory and that will be more specific.
- 07:55Carla, when your lab studies
- 07:58this innate immune response,
- 08:00this initial response that hey,
- 08:02there's something foreign in my
- 08:04body and that will help trigger
- 08:07the more adaptive response you had
- 08:09mentioned that you're looking at,
- 08:12kind of the magnitude and the
- 08:14duration of that innate response,
- 08:16but it seems that the innate response
- 08:20is a little bit shorter than
- 08:22the longer term adaptive response.
- 08:26So how important is the magnitude
- 08:28and the duration of the
- 08:31innate response and why did you choose to
- 08:34look at that?
- 08:36That's absolutely a very important question.
- 08:37So of course my answer will be that it is
- 08:40very important and let me elaborate why.
- 08:44So in the field we have learned by
- 08:46the time we were starting to
- 08:49focus on trying to understand what
- 08:52regulates the magnitude and duration,
- 08:54we already knew a lot about
- 08:56what triggers this innate immune response.
- 08:58And that was fundamental, right?
- 09:00So we understood the rules
- 09:02by which thee immune response
- 09:04is engaged, but as I was saying,
- 09:07this is the very first response.
- 09:09It's the one that tells us all we
- 09:12have a bacteria or we have a virus
- 09:14but cannot really distinguish between
- 09:16the type of bacteria or the type of
- 09:19virus and therefore is very broad.
- 09:22It doesn't really help us to only
- 09:24attack the bacteria or the
- 09:27virus or the parasite and it also can't,
- 09:29when a function is triggered,
- 09:31it can also
- 09:33induce what you could call collateral
- 09:35damage and it can affect your own cells.
- 09:38The classical example is that inflammation is
- 09:41a key part of this innate immune response,
- 09:44and as you can imagine,
- 09:46inflammation can be very good
- 09:47to help eliminate pathogens,
- 09:49but can also affect our own body.
- 09:51So we absolutely need this response when you
- 09:54get injured or when you have an infection.
- 09:57But the problem is what happens if you
- 10:00react way too much or if you react forever,
- 10:04and so that became a key interest
- 10:06of our lab trying to understand
- 10:08what dictates how much
- 10:10you should respond so that you can attack
- 10:13the pathogen but not yourself and how
- 10:16long you should respond so that once
- 10:18you have eliminated the passage and
- 10:20you don't keep on reacting against
- 10:23something that is not there anymore.
- 10:26So over the years we have been
- 10:28able to identify key breaks of
- 10:30the innate immune response.
- 10:33Why did you choose to look at
- 10:35the innate response and why is the
- 10:38magnitude and duration of that so
- 10:41important?
- 10:43As I was alluding, we
- 10:46require this very first innate
- 10:49response and at the time we started
- 10:52to become interested in understanding
- 10:54the regulation of the magnitude and the
- 10:57duration of the innate immune response,
- 11:00we already knew quite a lot what
- 11:02triggers this innate immune response.
- 11:04So that was fundamental work
- 11:06that allows us to understand
- 11:09that you need this response,
- 11:11but if features of this response as I was
- 11:15saying before is that it is triggered when,
- 11:18for instance, you encounter bacteria
- 11:20or a virus or parasite or fungi.
- 11:23But it's pretty broad and therefore
- 11:26it not only reacts against the
- 11:28microorganism or the macroorganism,
- 11:31but it can also affect your own self.
- 11:35For instance,
- 11:36a classic aspect of the innate
- 11:38immune response is what we
- 11:40usually call inflammation and so you
- 11:43can imagine that if this very broad
- 11:46immune response is way too high,
- 11:48or if it lasts forever,
- 11:50it can really induce what
- 11:53is known as collateral damage.
- 11:55It can really start affecting your own body,
- 11:58the way the system is built
- 12:01is that you kind of turn
- 12:04on this initial fire
- 12:06that then allows the induction of the more
- 12:09sophisticated adaptive immune response.
- 12:11But then you need to put off this fire,
- 12:14and that's when these molecular
- 12:16mechanisms that regulate how big
- 12:19the fire will be and how long
- 12:21the fire will be come into play.
- 12:23And you can imagine that then
- 12:25they become very important.
- 12:27You really need to regulate
- 12:28how much and the duration,
- 12:30so that then you don't start affecting
- 12:32your own self and this is what could
- 12:35happen in some type of diseases such
- 12:37as chronic inflammatory diseases or
- 12:40autoimmune diseases where you start
- 12:42affecting your own self.
- 12:44And so as
- 12:45we think about the implications for cancer,
- 12:48I mean what you're describing makes
- 12:50me think about things like hepatitis,
- 12:53where you can have hepatitis,
- 12:56which then causes inflammation
- 12:57and fibrosis and sets you
- 13:00up for hepatocellular carcinoma.
- 13:02Is that kind of the area that then
- 13:05brought you to thinking about cancer?
- 13:08Or where does the cancer angle come in?
- 13:12Yeah, that's a very very good analogy.
- 13:15So it turns out that absolutely,
- 13:17you're right.
- 13:18You have situations where you have
- 13:20this very chronic inflammation.
- 13:22This persistent
- 13:24activation of this innate immune response,
- 13:27and we know that chronic inflammation can
- 13:30absolutely increase the risk of some cancers.
- 13:32But the answer is not just
- 13:35so black and white.
- 13:36So what we're starting to learn is that
- 13:39there are different types of inflammation.
- 13:42One like the one you described,
- 13:44very well known to increase
- 13:46the risk of cancers,
- 13:47but there are other potential
- 13:49types of inflammation,
- 13:50and this is actually the area
- 13:52of much
- 13:53ongoing investigation in the whole field.
- 13:55What are the different types of
- 13:57inflammation that you have in cancer
- 14:00and how do they contribute to the
- 14:02concern and the analogy that I
- 14:04would make is that let's say you
- 14:06sometimes want to induce a little bit
- 14:08of this fire to mount a good
- 14:11immune response against the cancer,
- 14:12but you don't want to use too
- 14:15much that
- 14:16may be detrimental,
- 14:17so we are still at the level of
- 14:20trying to understand what are the
- 14:23different types of inflammatory
- 14:25responses in cancer and how they
- 14:28contribute to mount a good immune
- 14:30response against cancer or how they
- 14:33might contribute to actually favor
- 14:35cancer progression.
- 14:36And so when you're
- 14:39talking about mounting an
- 14:41immune response against cancer,
- 14:43it reminds me of things
- 14:45like immunotherapy.
- 14:47As we think about cancers
- 14:49and when we think about immunotherapy,
- 14:52we often think about revving
- 14:54up that immune system because so many
- 14:57cancers can hide from the immune system.
- 15:00So I wonder whether part of your
- 15:02work has to do with immunotherapy.
- 15:05But first we have to take a quick
- 15:08break for a medical minute,
- 15:10so please stay tuned for more information
- 15:13about immunotherapy and cancer
- 15:14with my guest Doctor Carla Rothlin.
- 15:17Support for Yale Cancer Answers
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- 15:23eliminate cancer as a cause of death.
- 15:26Learn more at astrazeneca-us.com.
- 15:29This is a medical minute about Melanoma.
- 15:32While Melanoma accounts for only
- 15:34about 4% of skin cancer cases,
- 15:36it causes the most skin cancer
- 15:38deaths when detected early,
- 15:40however, Melanoma is easily
- 15:42treated and highly curable.
- 15:44Clinical trials are currently underway to test
- 15:46innovative new treatments for Melanoma.
- 15:48The goal of the specialized programs
- 15:51of research excellence in skin cancer
- 15:53or SPORE grant is to better understand
- 15:56the biology of skin cancer with a focus
- 15:59on discovering targets that will lead
- 16:02to improved diagnosis and treatment.
- 16:04More information is available
- 16:06at yalecancercenter.org.
- 16:07You're listening to Connecticut Public Radio.
- 16:11Welcome
- 16:12back to Yale Cancer Answers.
- 16:14This is doctor Anees Chagpar
- 16:16and I'm joined tonight by my
- 16:18guest doctor Carla Rothlin.
- 16:20We're talking about immunotherapy
- 16:21for cancer and right before the break
- 16:24Carla, you were telling us about
- 16:26the work that goes on in your lab.
- 16:29Really looking at the innate immune
- 16:31response and the magnitude and duration
- 16:34of that response and I wonder
- 16:36how that really pertains to cancer.
- 16:38And right before the break,
- 16:40you mentioned that it's not
- 16:42only thinking about
- 16:43the inflammation and collateral
- 16:45damage that can occur that may
- 16:48predispose patients to cancer,
- 16:50but it's also in looking at
- 16:52the immune response that your
- 16:54body mounts against cancers,
- 16:56which makes me think more
- 16:58about immunotherapy.
- 16:59So can you talk a little bit about
- 17:02how that works and what work you've
- 17:06been doing in that regard in your lab?
- 17:10When we think about the immune response
- 17:14against cancer, I think it's very
- 17:16important to recognize that you
- 17:18know the immune response evolved
- 17:20to protect us against pathogens.
- 17:22So when we mount an immune response against
- 17:25something that has changed in our body,
- 17:27such as is the case of cancer cells,
- 17:31we're going to go through the same rules.
- 17:34So as I was saying at the beginning,
- 17:37the very first innate immune response
- 17:39is absolutely essential for allowing
- 17:41us to mount an immune response,
- 17:43for instance to a microorganism.
- 17:46And it turns out that of course
- 17:48is going to be essential to mount
- 17:51a good immune response to cancer.
- 17:54Now when we start analyzing the immune
- 17:56response that the body mounts against cancer,
- 17:59we realize that there are a fraction of
- 18:02patients in which the immune response has
- 18:05effectively occurred, and probably during the years,
- 18:08it has tried to control that cancer,
- 18:10and so in those patients in which
- 18:14the immune response has occurred
- 18:16it could be that maybe now the immune
- 18:19response is kind of tired,
- 18:21many people refer to it as exhausted,
- 18:23and what happens is that those
- 18:25cells that have the memory,
- 18:27those cells of the adaptive immune
- 18:29response that can really go and kill the
- 18:32cancer cell right as they would have done
- 18:35it if they were responding to a micronysm,
- 18:38now they're responding to a cancer cell.
- 18:40They can become tired,
- 18:41and so a large fraction of the current immunotherapies
- 18:44are centered on reactivating those
- 18:47for instance T cells,
- 18:49adaptive immune cells that have become tired,
- 18:52and this has been absolutely revolutionary
- 18:54in the treatment of patients.
- 18:56So you can see how understanding the
- 18:59fundamentals of the immune response
- 19:01has translated into effective new
- 19:03therapies for cancer patients.
- 19:05But it turns out that not all the
- 19:09patients have been able to mount a
- 19:11good immune response to the tumor.
- 19:14In some patients,
- 19:15there are no T cells to reactivate.
- 19:18They never were activated in the 1st place,
- 19:21and that's where our thinking came in.
- 19:23That's where turning on this you know,
- 19:26fire not too big,
- 19:27but turning it on a little bit
- 19:29might allow us to really keep the
- 19:32immune response against the cancer.
- 19:34And so a lot of current efforts in
- 19:37immunotherapy are centered on this
- 19:38initial response because we
- 19:40realized that in some patients it
- 19:43might not have occured.
- 19:45And so we need to turn this on.
- 19:48Or in some patients it may also
- 19:51have gotten tired and we need to
- 19:53reactivate it.
- 19:54So how exactly do you do that?
- 19:57Because I think when I think about
- 19:59cancer cells, I really think about
- 20:02normal cells that have gone awry,
- 20:04and so is it, perhaps that the body,
- 20:07especially in low grade cancers,
- 20:09cancers that look very
- 20:11much like normal cells,
- 20:12but that are just a little bit
- 20:15deranged that the body may not
- 20:18recognize them as being foreign.
- 20:20And how do you kickstart that
- 20:23innate response?
- 20:23We're talking about this very early stage,
- 20:26where cells are changing from being
- 20:28normal to to abnormal right from
- 20:31this premalignant to malignant stages
- 20:32and again our immune system,
- 20:35the innate immune system is very
- 20:37sensitive to changes in the tissue.
- 20:40So instead of recognizing changes
- 20:42in terms of mutations that may
- 20:44have arised in that cancer,
- 20:46Which is something that is much more
- 20:49recognized by the adaptive immune system,
- 20:52they can recognize if there
- 20:54has been a change in that issue.
- 20:57If maybe some cells are not
- 20:59functioning in the right way,
- 21:01and so those are things that we're
- 21:03very interested in understanding
- 21:04at the molecular level,
- 21:06what leads the activation
- 21:07of these innate immune cells?
- 21:09And then what is it that maybe
- 21:12changes that may appear
- 21:14like a wound that might affect
- 21:17the biology of these innate immune cells.
- 21:20Can you give us some glimmer into
- 21:23what those mechanisms are of actually
- 21:25kickstarting that immune system,
- 21:27because many of the people who are
- 21:30listening to this show are are thinking,
- 21:34that's great. You're studying
- 21:36it at the basic science level.
- 21:39But really, where we are interested in
- 21:42going is how do we actually conquer
- 21:46cancer at a patient level and so
- 21:50can you give us a sense
- 21:52of what are kind of the molecular
- 21:55mechanisms that you're looking at
- 21:58and how might we change those
- 22:01so that for actual patients we can
- 22:03potentially use this to make a difference?
- 22:06Absolutely this is where
- 22:09again basic science comes in.
- 22:11And I think this is where we need
- 22:14to understand fundamental biology.
- 22:16So the approach that we take is trying to
- 22:20understand what triggers this first response.
- 22:23To do this, we make use of models,
- 22:25sometimes it is not so easy to
- 22:28study this directly initially in a patient,
- 22:31but we can take models where we can induce
- 22:34for instance the transformation of a
- 22:36cell or we can induce an infection and
- 22:39this is very important because as I said,
- 22:42the principles are going to be pretty
- 22:44much shared with the immune response to
- 22:46infection and so in these models which
- 22:49are in many occasions animal models,
- 22:51what we try to do is to
- 22:54try to detect how the cells of the
- 22:57innate immune system these first
- 22:59responders react to a cell that is
- 23:03changing either because there has
- 23:05been an infection and a wound or
- 23:08because it's has been mutated and so
- 23:10we do this with advanced techniques
- 23:13that allow us to understand what
- 23:15is changing in the immune cell.
- 23:18Now a very important aspect
- 23:20I think is to then try to go to
- 23:23patient samples and understand whether
- 23:25those features that we saw change in
- 23:29the context of an infection or in
- 23:32the context of a model of cancer
- 23:35in an animal model,
- 23:36are also detected in the context of
- 23:39a transformation of a cell and the
- 23:42response to this in the patient.
- 23:44So I think going from this very
- 23:46fundamental basic approaches to taking
- 23:48some translational approaches and
- 23:50trying to understand whether the same
- 23:53changes are observed is very important.
- 23:55But then again,
- 23:56I think we need to go back to the
- 23:59experimental models because once we
- 24:01understand what those changes are,
- 24:03we would like to
- 24:04intervene and modulate
- 24:06them so we can maybe turn on
- 24:08that fire a little bit more.
- 24:10Maybe induce that immune response a
- 24:12little bit more, and to do that again,
- 24:14we need to go to the model.
- 24:16So we start with the model, we validate
- 24:19and understand whether it is the same
- 24:21in a human setting and then we go back
- 24:23to the model to try to understand how
- 24:25we can change it to make it better.
- 24:27And it is this iterative type of
- 24:30experimental approach
- 24:32from the model to human samples
- 24:34to the model that has led
- 24:35to a lot of new ways to change the
- 24:38immune response and I am confident
- 24:39that we will allow us to understand
- 24:42what we need to change in those
- 24:44patients that have mounted an
- 24:46immune response to cancer.
- 24:48So tell us more about some of these
- 24:51interventions that you've tried and how
- 24:53they work in in the models and and what
- 24:57prospects there are to actually having
- 25:00the same intervention in patients.
- 25:04And then just as a second
- 25:06piece to that question,
- 25:08when you talked earlier
- 25:10about this collateral damage,
- 25:12you wonder about when you
- 25:14actually take that into patients.
- 25:16Whether there will be collateral
- 25:18damage as well as you
- 25:20continue to light that fire,
- 25:22or whether you've really gotten
- 25:23it down to the point where you
- 25:26can modulate that very well
- 25:27to limit that collateral
- 25:29damage.
- 25:30Let me give you this with an example.
- 25:34So as I said, we try to understand
- 25:36what are those ways to regulate right?
- 25:39The magnitude and duration.
- 25:40And again, we went from the animal models to
- 25:43some human samples.
- 25:45And in doing that we identified
- 25:47genes that encode for molecules
- 25:49that are those regulators.
- 25:51And some of those genes and then
- 25:54those proteins that are encoded by
- 25:56this gene are a key focus of our
- 25:59lab and they're called TAM receptors.
- 26:01Tyrosine kinase is the interesting
- 26:03aspect of this is, as I said,
- 26:05they are like the brakes of this
- 26:08innate immune response.
- 26:10And these proteins can be targeted by drugs.
- 26:14So these proteins are in
- 26:17innate immune cells and when you
- 26:20activate this protein it will act as
- 26:23a break of this innate immune cell.
- 26:26It will put down this fire.
- 26:29What we can do is we can work
- 26:32and develop molecules that inhibit
- 26:34the function of this protein.
- 26:37Or we can also generate animal models
- 26:40that do not even have this protein.
- 26:44And so what you would predict is that
- 26:47if you do not engage this break so well,
- 26:50you will mount a better fire,
- 26:53so we will be able to regulate
- 26:55the magnitude of this response,
- 26:57and so that's what we have discovered.
- 27:00And so going from the animal
- 27:02models to human cells,
- 27:03we now know that we can use small
- 27:06molecules that inhibit this proteins,
- 27:08and that allows a better fire.
- 27:10And we know that in animal
- 27:12models these can lead
- 27:14to the ability of these
- 27:16animals to mount a much
- 27:18better immune response against cancer.
- 27:20So we are actually right now at the
- 27:22process of starting to translate this
- 27:25into humans through investigator
- 27:27initiated clinical trials.
- 27:28Actually here right here
- 27:30at Yale Cancer Center,
- 27:32so we can try to understand whether
- 27:35these drugs, which we know are safe,
- 27:37can ignite just a little bit more
- 27:41this fire and you asked me the question,
- 27:45how do I ensure that
- 27:47it's not a big fire that
- 27:49will induce collateral damage?
- 27:51That's a very very important
- 27:52question to answer.
- 27:54I think that brings me back
- 27:55to my initial training,
- 27:57which was really in pharmacology,
- 27:58in Neuropharmacology, but I learned,
- 28:00I think a lot about pharmacology,
- 28:02and that's where drugs
- 28:04give you the ability to
- 28:06think a lot about the dose is the
- 28:08regimens, how you're
- 28:10going to try to modulate this in vivo
- 28:13and that becomes very important.
- 28:14So how much you would give
- 28:16of this drug may be
- 28:18whether you will deliver it just
- 28:20to the tumor site so you don't
- 28:22start a fire everywhere,
- 28:24and that's an aspect that will
- 28:25be very important into making
- 28:27sure that this can truly help the
- 28:30patients eliminate the cancer and
- 28:31not induce fires in places that we
- 28:34don't want to.
- 28:35Doctor Carla Rothlin is Dorys McConnell Duberg Professor
- 28:38of Immunobiology
- 28:39and professor of Pharmacology
- 28:41at the Yale School of Medicine.
- 28:43If you have questions the addresses
- 28:45cancer answers at yale.edu and
- 28:47past editions of the program are
- 28:49available in audio and written
- 28:51form at yalecancercenter.org.
- 28:52We hope you'll join us next week to
- 28:55learn more about the fight against
- 28:57cancer here on Connecticut Public Radio.