Cancer Vaccines: Training the Immune System to See Cancer

Just like each patient, each cancer is unique. While patients have traditionally been treated in a one-size-fits-all manner, doctors’ ability to treat patients in a personalized manner that’s most likely to benefit them has improved significantly in the past several years.

One of the most promising personalized immunotherapy approaches currently being explored in the clinic is cancer vaccines. These vaccines—especially patient-tailored versions known as neoantigen vaccines—are capable of educating patients’ immune systems about what their individual tumors “look like,” and in turn, have the potential to improve the immune system’s ability to target and eliminate cancer.

In this webinar for patients and caregivers, Gavin Dunn, MD, PhD, of the Siteman Cancer Center at Washington University in St. Louis, will provide an in-depth discussion of these cancer vaccines focusing on topics including but not limited to: how they’re made, how they’re being used today, and how advances currently being explored might soon make them even more beneficial for cancer patients.
 
Dr. Dunn is currently an assistant professor in the Department of Neurological Surgery, and a member of the Center for Human Immunology and Immunotherapy Programs at the Siteman Cancer Center at the Washington University School of Medicine in St. Louis. He is also currently a CRI-funded CLIP Investigator.

As both a practicing oncologist and the head of a research laboratory, Dr. Dunn is devoted to helping patients with malignant brain cancer, especially glioma. On the clinical side, Dr. Dunn is heavily involved in ongoing clinical trial efforts that are evaluating novel immunotherapies, including vaccines, for brain cancer patients. To complement his clinical efforts, the work being done in Dr. Dunn’s laboratory—currently supported in part by a Cancer Research Institute CLIP grant—aims to provide a better understanding of the genetics of brain cancers and how they interact with the immune system, in order to enhance the effectiveness of vaccine strategies. Ultimately, his goal is to leverage this knowledge to develop and refine novel immunotherapy approaches that can help improve survival for patients with this hard-to-treat cancer type.

The "Cancer Immunotherapy and You" webinar series is produced by the Cancer Research Institute and is hosted by our science writer, Arthur Brodsky, PhD The series is made possible with generous support from Bristol-Myers Squibb, with additional support from Regeneron, Sanofi Genzyme, and Adaptimmune.

Browse our Cancer Immunotherapy and You Webinar Series playlist on YouTube or visit the Webinars page on our website to see other webinars in this series.

WEBINAR TRANSCRIPTION

Arthur Brodksy, PhD:

Hello. Welcome to the Cancer Research Institute Cancer Immunotherapy and You patient webinar series. Today is Tuesday, September 18. And the title of today's webinar is Cancer Vaccines– Training the Immune System to See Cancer. 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 Regeneron, Sanofi Genzyme, and Adaptimmune.

My name is Arthur Brodsky. And I'm the science writer at the Cancer Research Institute, a nonprofit organization established 65 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. Gavin Dunn is currently an assistant professor in the Department of Neurological Surgery and a member of the Siteman Cancer Center, as well as the Center for Human Immunology and Immunotherapy programs at the Washington University School of Medicine in St. Louis. He is also currently a CRI-funded CLIP investigator.

As both a practicing oncologist and a researcher, Dr. Dunn is devoted to helping patients with malignant brain cancer, especially glioma. On the clinical side, Dr. Dunn is heavily involved in ongoing clinical trial efforts that are evaluating novel immunotherapies, including vaccines, for brain cancer patients.

To complement his clinical efforts, the work being done in Dr. Dunn's laboratory aims to provide a better understanding of the genetics of brain cancers and how they interact with the immune system in order to enhance the effectiveness of immunotherapies, including vaccines. Ultimately, his goal is to leverage this knowledge to develop and refine the novel immunotherapy approaches that can help improve survival for patients with this hard-to-treat cancer type. Dr. Dunn, it is an honor to have you with us here today.

Gavin Dunn, MD, PhD:

Great. Thanks a lot, Arthur. This is a really terrific series. And I'm really, really happy to be a part of it. So let's just get right to it. This topic is about cancer vaccines. And this is a very exciting area of clinical study. And what we hope to do today is provide an overview of what they are and where we might be going in this space.

So let's take a step back here in just ask a general question of what vaccines actually are. And simply defined, vaccines help teach the immune system about what threats or challenges might look like so that the immune system can target and eliminate them. And it's likely that you've encountered vaccines really mostly in the preventative setting, as in childhood vaccines against diphtheria, tetanus, et cetera.

And the reason that vaccines can be effective against some of these microbes or pathogens that we just talked about is that there are components of bacteria and viruses that look very foreign to the immune system and thus are easily recognized. Sometimes there are components of these bacteria that are used in vaccines, or sometimes inactivated forms. But we have really evolved to recognize these entities. And thus we are able to do a very good job of vaccinating against these problems. And I would point out that immunization and vaccination is really one of the amazing success stories of modern medicine.

Now, when we talk about cancer, let's switch to a different way to think about vaccines in terms of therapeutic vaccines rather than preventative vaccines generally. Now, cancer cells are a lot more like our own cells than bacteria and viruses. And in fact, most of what makes up a cancer cell is very similar to a normal cell. But there are some features about cancer cells that we can identify and then hopefully leverage to target them immunologically. And so, again, the point of this discussion today is to think about how vaccines can be designed against cancer targets.

And now, to understand how we can target cancer cells as different from normal, it's really important to think about what the basis of what that targeting strategy might be. From a very general standpoint, any medication that is used in oncology, be it chemotherapy or these types of immunotherapies, are trying to take advantage of distinctions between normal cells and tumor cells– that is, do something to control or eradicate tumor cells and do as minimal risk to normal cells as possible.

So tumor cells or cancer cells are collections of alterations of DNA. And the DNA is what our genome encodes. Now, if this is disrupted– and that could be in the form of mutations or differential expression– then this can lead to the production of abnormal proteins, abnormal cell signaling. And that can promote and support the development of cancer and its aggressive behavior.

So what about these differences, then, can be targeted in a cancer vaccine? There are several categories of targets. And when I say "target," what I mean is just what a vaccine might be designed against.

So in some cases, these targets are very similar between normal cells and cancer cells. They're just expressed differently, meaning they're more abundant in tumor cells or they're expressed at the wrong time in the wrong cell type. But there's not a mutation in them.

And there are actually some very good examples of these that are very active in clinical trials, proteins like NY-ESO-1, the MAGE family of proteins. These are just names of these over-expressed and really dysregulated proteins. MAGE is actually one of the first proteins that was discovered to be recognized by the immune system in a tumor cell in the mid-1990s.

So this has really opened the field with that family of proteins. HER2 and TW1 are other examples. And in fact, one of the FDA-approved vaccine approaches, called PROVENGE, for prostate cancer use these types of wild-type over-expressed proteins.

The second group that I want to talk about– and really, we're going to spend a lot more time talking about for the rest of this discussion– are very cancer-specific targets. And those are targets that are these mutations in tumor cells that are not found in normal cells. And I would just bring up one point of nomenclature here without digging into the weeds too much to really describe this term "neoantigens." And I want to just really break that down.

So "neo" points to "new." And these are mutations that are arisen in the tumor cell that did not exist in any of the rest of the cells of a patient during immune development and prior to the development of the tumor. So an antigen is what is presented to the immune system and can be recognized by the immune system.

So neoantigens are really new antigens that, as just described, are present in the tumor and are not present anywhere else. And just to describe that in a little bit more immunologic context, our immune systems develop to not attack ourselves. And so if those mutations were not present when our immune system developed, then our immune systems will not be tolerant to those mutations.

And so therefore, they are compelling vaccine candidates because our immune systems are not tolerant to them. And they are specific to the tumor because they're not present in normal cells. So I think that's a really important point. And this notion of neoantigens will be really a big part of the discussion in the next few slides here.

And most importantly when we talk about neoantigens, these mutations that we find in tumors are often very different from patient to patient. And while some tumors share a couple of the same mutations, most of the mutations are very different. And it's highly unlikely that the tumors from one patient to another are going to share the vast majority of those mutations.

And so really, when we're talking about neoantigens, we're talking about a very personalized approach to cancer vaccines that differs from patient to patient. So one patient's vaccine will be produced and target a different set of antigens than another patient’s. And so this is personalized immunotherapy is what we're talking about with cancer vaccines against neoantigens.

So how do we go about designing cancer vaccines as we talked a little bit about the basis of them? Well, step one– and these steps are shown here in the slide. Step one is that we actually have to analyze the tumor. And that can come in several different forms.

Really, every time a diagnosis is made, some part of that tumor has to be obtained by a biopsy or a more aggressive surgery. And so we can do some pretty comprehensive evaluation of that tissue to look at, what are those mutations in the DNA? And are they expressed? Can they become proteins by looking at the RNA, or the Ribonucleic Acid?

And so once we have all that information, that process actually goes fairly quickly now. And there's been a lot of technological development around that over the last decade or so. Once we have that information, there is an ever-growing number of ways to look at that and try to discern which of those mutations might be most recognized by the immune system.

Because it's those neoantigen candidates or those targets that– when we go to step three here– are going to be included in the manufacturing of a vaccine. And we'll talk a little bit more expansively here a little bit about what types of vaccines can be made with that information. But whether it's peptide or whether it's DNA, the targets are really all the same.

And once that vaccine is manufactured, then step four is the administration of that vaccine. And really, I would say 4A and 4B here would be– the administration would be 4A. Then 4B is– we want to monitor over time the immunoresponses that patients may mount to those vaccine targets to see if the vaccine is being effective. And of course, monitoring patients for their clinical response with the types of scans that patients usually get as well is a big part of that process.

So let's drill down a little bit more about what we anticipate would happen when a patient is vaccinated with a personalized vaccine. So as you can see in this slide here, each of these red triangles represents a neoantigen target that is one of usually a number of targets that the vaccine comprises.

And really, you won't usually see a vaccine against one target. You're going to see what we would call a "polyvalent vaccine," or a vaccine that targets a number of different things. So that vaccine is administered by any number of routes, which we'll get to a little bit later.

And it's really important that these vaccine products are seen and taken up by key cells of the immune system, such as dendritic cells. And dendritic cells are really important nodes of the immune system that take up foreign material and are extremely good at presenting that material to immune cells that are always trafficking or serving around our bodies, particularly in our lymph nodes.

So if these dendritic cells are able to take up that material, as you'll see in the next slide, then these then get presented by the dendritic cell on its cell surface in some specialized molecules called MHC molecules, or Major Histocompatibility Complex molecules. And the best way to think about these are these are the type of molecules that clinicians look at when we're talking about transplant. So these are HLA molecules, just to give you the human ortholog here in clinical trial and patient care settings.

So if these neoantigens are presented by these HLA molecules, then T cells that are specific for these antigens can recognize that complex. And you'll see the T cell has what looks like two chains here. And that is a T-cell receptor. So a T-cell receptor then has to recognize that complex together.

And if that T-cell receptor is specific for that complex, then importantly, those naive T cells or memory T cells can be activated or reactivated depending on what their cell state is. And then that's the key. The whole point of these vaccines is to activate T cells or T lymphocytes that are specific for these antigens in tumors. And once those cells are activated, we anticipate and we hope that those T cells then home back to the site of the cancer, recognize that antigen presented by the cancer cell.

Now, remember, it's the same antigen in that the dendritic cell was recognizing from that vaccine. Now the T cell is recognizing that antigen really in the most native state, which in the site of the tumor, and then controlling and eliminating that tumor cell. So that is the pathway that we hope immunologically happens once vaccines are administered if they are successful.

And so just to summarize some of the steps that we hope immunologically take place here, we hope that these neoantigen vaccines can stimulate new T cell responses against cancer. Now, there may be some pre-existing responses that vaccines may also boost or augment. And interestingly, what these vaccines may do is hopefully increase the responses that T cells can have against other antigens in a tumor cell that perhaps were not targeted initially by the vaccine.

And I think that the other point I would mention here is that you could anticipate that you could do this a few times. Once one vaccine is made, this can be something that could be done in an iterative fashion. But that is at a very early phase.

Now, as with many immunotherapy types, vaccines are the most advanced, and we know the most about their clinical responses and their immunologic effects in patients with advanced or metastatic melanoma. Again, there is a very rich and important history of immunotherapy in this disease type.

So vaccines have been described in very important publications from Ugur Sahin’s group and Cathy Wu's group have showed very interesting immunologic responses and, in some cases, encouraging clinical responses, too. I would be careful to say that these are early phase studies.

And certainly larger studies are ongoing in this type, but also other tumor types as well. And you can see those tumor types listed here. I'm a neurosurgeon. I studied glioblastoma. Certainly we and other groups have activities in this area– breast cancer, colorectal cancer, liver cancer, pancreatic cancer, pediatric cancers, hematologic malignancies.

Really, there is a lot of interest in this area because it is personalized. This approach is specific. And again, the last few years has seen a lot of very clinically important excitement around immunotherapy. And this is one example of that.

As I said, we are at an early stage in these vaccines. But there's a lot of important exploration going on. There are a number of important questions in this space. And some of them are listed here on the slide, as you can see.

One, certainly improving how vaccine targets are identified in patients is really important. We want to identify the targets that are the most appropriate to hit with vaccines. And that's really, really important. There are many ways to deliver vaccines and also compose these vaccines. And we'll talk about that a little bit.

And then I think it's really important– with many oncology approaches, but especially with immunotherapy, often we are talking about how to combine these rationally and intelligently with other forms of immunotherapy or non-immunotherapy agents. And we're at a very early stage of understanding how to rationally deploy those combinations, too.

Arthur Brodksy, PhD:

All right. Well, thank you very much for that great overview of vaccines, Dr. Dunn. So now we have a little time for some question and answer, a question and answer session where hopefully we can dive a little bit more into the details.

Gavin Dunn, MD, PhD:

Sure.

Arthur Brodksy, PhD:

So you mentioned at the end that obviously, our understanding of how to make the most effective vaccines is constantly advancing. But given what we know now, are there ways that doctors can determine the patients who might be most likely to benefit from a vaccine?

Gavin Dunn, MD, PhD:

Arthur, that's a great question. I think a couple point of thoughts come up with that type of consideration, the most important of which is that in order to compose a vaccine and think that a vaccine will help a patient's particular situation, vaccines need targets. And when we think about different types of tumors– and the previous slide mentioned a number of these, melanoma, breast, et cetera– they all don't have the same number of mutations.

And when we're talking specifically about neoantigen vaccines, mutation number is the generator for neoantigen targets. So if a tumor has very few mutations, it's very likely not going to be a great target for neoantigen vaccines. There may be some tumor-associated candidates that could demarcate that tumor as an appropriate vaccine target. But as a neoantigen target, tumors with a very low number of DNA mutations may not be the best.

Conversely, there are tumor types such as lung, such as melanoma, such as head and neck squamous cell carcinoma– because they're carcinogen induced, they have a lot of mutations, and therefore likely a higher number of candidates. So those patients a priori may at least have the targets needed to generate a vaccine.

Secondly, I would say that we've seen there are some tumor types that have been particularly responsive to some checkpoint blockade therapy agents. At the risk of extrapolating– for example, melanoma and lung, et cetera– these are tumor types in which immunotherapy does have a signal. At least one can speculate that the immune system in some way can be effective in those settings. And this may go back to our first point about their number of mutations, and therefore neoantigens.

The final point I would make is that the clinical situation of the patient does come into it. The one thing I think that's really important to think about is the kinetics of what the immune response is in the immunotherapy state.

Because one is doing something to then activate the immune system to then act on the tumor, it does take a little bit of time to develop. And therefore, if there is a clinical situation in which there's mass effect involved or something that needs to happen to shrink some mass effect very quickly, those patients may need some other intervention before an immunotherapy approach that could take a little time to develop. It is most clinically reasonable to consider.

Arthur Brodksy, PhD:

I understand. I think that makes good sense. So I wanted to follow up on that. You're talking about from the doctor's perspective how they might be able to identify patients who are likely to respond. I want to look at it from the other perspective, from the patient side of things.

And again, because none of these personalized vaccines are FDA approved yet, they wouldn't be a standard treatment that a patient would get. So they would have to receive it in a clinical trial. How do patients– in what ways can they go about determining if maybe they would be eligible for a cancer vaccine clinical trial?

Gavin Dunn, MD, PhD:

That is a great question. And when I think about that question, I think one way to think about it is there are almost three points to a triangle here. So first, patients and families are really aggressive advocates.

And certainly, I have found it very common that patients will look on resources like clinicaltrials.gov and identify the clinical trial settings that you just described very nicely to see what studies are open and then contact whoever is listed as the contact– that can be a clinical research coordinator or the investigator– directly. So that's one point of that triangle.

The second is certainly the treating oncologist. Most oncologists attend meetings like the American Society of Clinical Oncology. And even if that study is not open, they are often very well connected with other oncologists in his or her field and therefore may also be a very good resource from the oncology side.

But the third point– and I think this really gets to some of the resources of the CRI– is that there are other nonprofit educational resources that are out there that can also be advocates for patients, like the Clinical Trial Finder on the CRI website. And also, patient summits through the CRI bring lots of patients together with cutting-edge oncologists and providers that may make a connection in an interface that the first two points perhaps did not. So I think those are three ways to have patients connect with the clinical trials for these types of vaccines.

Arthur Brodksy, PhD:

Right. And I think that is a very important point you brought up with our clinical trial finders and our patient summits, which help to educate and empower patients with that, which we'll get to a little bit later.

So now I'd like to talk a little bit about how the vaccines are actually given. I know for simplicity's sake in the diagram, it was just that shot providing the vaccine. And I think, like you mentioned, most of us are used to vaccines in that context– as shots. So cancer vaccines– are they given as shots, too? Or are there other ways to administer them?

Gavin Dunn, MD, PhD:

Sure. It's possible that a lot of roads lead to Rome here, meaning a lot of different approaches may lead to the same type of immune stimulation that cancer vaccines are trying to accomplish. And as you pointed out– and I think the diagram illustrated that very well– that often, these are administered in a subcutaneous or intramuscular way and often represented as strings of small pieces of proteins. And we would call those "peptides" that are little fragments of proteins. The immune system really recognizes those well.

But there are certainly other formulations of vaccine that have been studied and are being studied. For example, for patients with brain tumors, Linda Liau's group at UCLA has a significant body of work around lysate from tumors. And what I mean by that is taking the tumor cells and kind of grinding them up so that they're not a membrane in a cell anymore. But they're just sort of collections [AUDIO OUT] vaccines in that way. And this is still an active area of clinical study.

And other formulations– DNA and RNA have their own separate advantages and are also being studied. I would say that most of these approaches are trying to distill which of the targets are important within these DNA alterations when we're talking about neoantigen vaccines. And it's a little bit too early to know which of these will be the most effective. And also, just from a feasibility standpoint, which can be manufactured in a time frame that is most helpful for patients?

But certainly, there are publications around each of the formulations we just talked about– lysate, peptide, DNA, RNA. There are also ways to package these types of candidates in virus vectors. And that is a very rapidly growing area of study in the viral therapy interface with immunotherapy.

So I think the next few years will perhaps either lend some clarity to which of these may be more suitable or suggest that they all do a pretty good job. And then more pragmatic characteristics come into play, such as ease of production and things like that.

Arthur Brodksy, PhD:

I think that's a great point because obviously we've seen a lot of results– not necessarily in patients, but in the pre-clinical setting– about the promise and the potential that these vaccines have. But as you mentioned, there are those other considerations. It's one thing for a lab to make a few samples in the lab. But then there's different challenges when it comes to producing that for patients, especially at that larger scale, to make sure they can have it in a timely and also an affordable fashion.

Gavin Dunn, MD, PhD:

Right. I think that is a really important point. And really, the way that one can really think about it is it's a new drug for every individual patient. And so that personalized production, as you just pointed out, is a really key component.

Arthur Brodksy, PhD:

OK. And at the end of the challenges slide, one of the last things you touched upon was combining vaccines with other immunotherapies and the potential of that. Especially, I think you referred to the checkpoint immunotherapies, which have been very successful on their own.

Could you talk about the checkpoint immunotherapies, as well as the other treatments, such as chemotherapy or radiation, that might go to augment that activity? Could you talk a little bit more about how these other treatments when combined with vaccines can improve the activity of those vaccines, as well as some strategies that doctors are using to determine which immunotherapies might combine to be the most effective?

Gavin Dunn, MD, PhD:

Sure. Again, I would just preface this answer by saying that there is a lot of work being done preclinically in the basic science space. But I think you alluded to this point very well, which is that that body of knowledge does not always translate into something that's totally effective for patients. But of course, that's the most important thing.

Now, when it comes to combinations, some of this is related to what are the immunotherapies that are already FDA approved and therefore can be combined with investigational agents. And so I think the checkpoint blockade, meaning the either anti-CTLA-4 ipilimumab or the anti PD-1/PD-L1 agents like Keytruda, et cetera– because those agents are FDA approved in really an ever-growing number of indications and number of cancer types, then from the standpoint of being able to do a clinical trial and think about what might be FDA approved, it's very prudent to be able to combine something with something that's already FDA approved, already has safety, already has some level of activity.

And that's not just an answer that around pragmatism because I think Dr. Cathy Wu's paper on melanoma vaccine in some patients who were administered a vaccine– and then their response had essentially slowed and then received an anti-PD-1 agent on top of that. Then their clinical response really was reignited and restored. I think that there's nothing like data and patients to support pursuing a particular combination. I think that was very compelling and very interesting data.

You could also imagine mechanistically how that would work. There were antigen-experienced cells that had been primed by the vaccine. And then their activity for some reason or another had waned. And then therefore, when their checkpoints were released later in their clinical course with that anti-PD-1 agent, then their efficacy and activity was restored.

So it makes sense not just from a let's combine a plus b. But it did make sense from an immunological and mechanistic point of view. And ultimately, you do want these types of things to have some type of compelling biological rationale and immunological rationale.

I think when it comes to chemotherapy and radiation, it's just a little hard to know how to balance what you might be doing to stimulate the immune system in combination with the vaccine with some of the things that they can do to suppress our immune response, too, like we know some conventional chemotherapies can.

And so taking advantage of their immunostimulatory properties, perhaps in ways that are not therapeutic in the way that we usually think about chemotherapy– these may be administered in what we would call "sub-therapeutic doses" that may have an immunological effect but not a clinical effect in isolation. But this is a synergy when you combine it with something that's immunopotentiating.

So I can see that the combinations that are immediately in front of us are vaccines combined with some type of checkpoint blockade. Now, we know that that's a tip of an iceberg, too. And that's mostly exciting, actually, in that there are a number of other checkpoint agents that will be coming online over the next few years.

But we've seen that the PD-1/PD-L1 agents do have a good response. But there are a number of patients who don't respond. And it's compelling or appealing to think that if you then add a vaccine to that, you may increase that, especially in agents that are already FDA approved.

Arthur Brodksy, PhD:

So we're almost out of time. But before we wrap up, I just wanted to give you one last chance to describe– you mentioned, obviously– and I think we both feel this way– that there is so much promise but also so many questions that we need to answer before we can get these patient benefits to the level that we want them to be at. So given that, I just want to give you one last chance to maybe talk a little bit about your vision and your hopes for the field of cancer vaccines.

Gavin Dunn, MD, PhD:

Yeah. I think it's a very exciting time for cancer immunotherapy, as you alluded to. And the outcome that everybody wants is to help as many patients as absolutely possible. And immunotherapy has clearly demonstrated the potential for that, especially over the last five years. And the cancer vaccines we've described really are the type of personalized approaches that oncology has been trying to go in one form or another for really the last 5 to 10 years.

They may not be the answer for everyone. And when we talk about immunotherapy, we know that there are a number of divisions within immunotherapy. There's checkpoint. There's CAR T-cell therapy. There are vaccines. And I think it's going to be really important to understand how best to stimulate immune responses with these types of vaccines and then to figure out which of those patients who may benefit from immunotherapy in particular are going to benefit best from a vaccine compared to another type of immunotherapy.

And I think we touched on a lot of important points from your discussion. I think doing this in concert with advocates that can point to clinical trial settings in this area are really important. Again, I think this is a great series. And I really appreciate you having me.

Arthur Brodksy, PhD:

Very much our pleasure. It's great to hear about how promising this area of immunotherapy appears to be for patients. And hopefully more and more patients are able to soon benefit from this approach. So that is all the time that we have for today. Thank you so much, Dr. Dunn, for your extremely informative webinar. I learned a lot. And I hope that everyone else watching out there learned as well.

For more of our webinars and additional resources that we have for patients and caregivers as part of CRI's Answer to Cancer educational programs, we encourage you all to check out our website at www.cancerresearch.org. Here, you can read and watch stories that are shared by others who have received immunotherapy treatments across a wide variety of cancer types. You can register for one or more of our immunotherapy patient summits.

You can browse our entire library of past webinars, featuring the world's leading immunotherapy experts, such as Dr. Dunn. You can access information on other resources, including treatment, emotional support, and financial assistance. And last but not least, you can find help when it comes to locating an immunotherapy clinical trial that might be right for you.

So with respect to the patient summit series, on June 30, we kicked off our patient summit series this year in San Francisco. And at these free half-day events, we connect patients and caregivers with immunotherapy experts to allow them to discuss the latest advances in research and treatment. Other summits are scheduled this year for New York City, San Diego, and Houston. And please go to cancerresearch.org/summit to learn more and to register to attend.

Finally, I'd like to thank our sponsors one last time for making this webinar series possible– Bristol-Myers Squibb, Regeneration, Sanofi Genzyme, and Adaptimmune. I would 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 cancerresearch.org/webinars to learn more about the immunotherapy options in a number of cancer types.

Dr. Dunn, I just wanted to thank you so much again one last time for taking the time today, and as well for the amazing work that you are doing to help patients. We wish you the best of luck.

Gavin Dunn, MD, PhD:

Thanks a lot, Arthur. I appreciate it.

Arthur Brodksy, PhD:

Thank you. Take care.