Exploring the Future of Cancer Immunotherapy, with Dr. Nina Bhardwaj

The field of cancer immunotherapy has achieved great progress already in 2023. With each passing day, new advancements and discoveries fuel hope that even greater breakthroughs are within reach, bringing renewed anticipation for what’s on the horizon.

To illuminate these remarkable developments, we spoke with renowned immunologist Nina Bhardwaj, MD, PhD, of the Icahn School of Medicine at Mount Sinai, as part of our Cancer Immunotherapy and You™ patient education webinar series.

In this webinar, Dr. Bhardwaj explores strides made in personalized immunotherapies as well as the technologies behind these new treatments and research avenues. Most notably, she highlights recent results relating to neoantigen vaccines, which target the unique, patient-specific mutations that characterize individuals’ tumors. In addition, she emphasizes the impact of new sequencing and spatiotemporal analysis tools that are helping to unravel more of cancer’s complexities, improving our understanding and clinical capabilities, including early detection methods.

Dr. Bhardwaj also discusses the significance of biomarkers in predicting responses to immunotherapy and managing potential side effects. Additionally, initiatives aimed at enhancing health equity and accessibility to clinical trials emerged as critical focal points, highlighting the necessity of inclusivity in advancing cancer research for marginalized communities.

The convergence of cutting-edge research, technological advancements, and informed clinical expertise has set the stage for an era where cancer immunotherapy holds the potential to transform lives and reshape the future of oncology. To learn more about the valuable insights shared by Dr. Bhardwaj, we invite you to watch the full conversation in the video interview below.

A former CRI fellow and current associate director CRI Scientific Advisory Council, Dr. Bhardwaj has been named one of Scientific American’s Top 50 Researchers. Currently, she is the director of immunotherapy and co-director of the cancer immunology program at Mount Sinai’s Tisch Cancer Institute. Additionally, she is the Ward Coleman Chair in Cancer Research as well as a Professor of Medicine and Urology at the Icahn School of Medicine at Mount Sinai.

The Cancer Immunotherapy and You™ webinar series is produced by the Cancer Research Institute and is hosted by our associate director of scientific content, Arthur N. Brodsky, PhD.

TRANSCRIPT (edited for length and clarity)

Arthur Brodsky, PhD 

Hello, and welcome to the Cancer Research Institute “Cancer Immunotherapy and You” patient education webinar series. I’m Dr. Arthur Brodsky, associate director of scientific content at the Cancer Research Institute.

During today’s webinar, we’ll be focusing on “Cancer Immunotherapy: 2023 Research and a Look Ahead.”

Now, it is my pleasure to introduce today’s expert. Dr. Nina Bhardwaj, MD, PhD is the Director of Immunotherapy, Medical Director of the Vaccine and Cell Therapy Laboratory, and Co-Director of the Cancer immunology Program at the Tisch Cancer Institute. Additionally, she is the Ward Coleman Chair in Cancer Research as well as a Professor of Medicine and Urology at the Icahn School of Medicine at Mount Sinai. Dr. Bhardwaj is also a former CRI-funded fellow, and now an associate director of our Scientific Advisory Council, and she has made seminal contributions to human dendritic cell biology. In addition to being named one of Scientific American’s Top 50 Researchers, she has also received the CRI Frederick W. Alt Award for New Discoveries in Immunology.

Welcome, Dr. Bhardwaj, and thank you for joining us!

Nina Bhardwaj, MD, PhD

Thank you so much. It’s a pleasure to be here. I’m delighted to discuss the future of immunotherapy and cancer with you today.

Arthur Brodsky, PhD 

We just got off of a big meeting at AACR 2023. What, in your opinion, have been the most important advances in cancer immunology and immunotherapy in 2023 so far?

Nina Bhardwaj, MD, PhD 

I’m probably a bit biased in this respect, but I think the exciting features of the AACR meeting were centered around the use and discovery of novel cancer antigens and their incorporation into vaccines. In particular, vaccines in the prevention setting, to prevent recurrence of cancer,  was one of the highlights.

There was a lot of progress made on identifying new molecules that can be targeted, which are expressed by cancers, and which can be combined with current therapies to further improve their ability to suppress cancer growth. Many of you out there are probably aware of the checkpoint therapies. These are antibodies that target inhibitory molecules on immune cells as well as on cancer cells, and which are designed to reawaken the immune system. Some of these have been in the clinic for many years, and now we have a whole new set of such molecules that have been discovered. These molecules are now being targeted by either antibodies or small molecules that can be used in combination to further advance the effectiveness of these earlier interventions.

There’s also a major effort to deconvolute the tumor microenvironment. When a tumor is growing, it’s not just made up of tumor cells. It attracts immune cells, some of these immune cells become dysregulated and become partners to the tumor cells that can help tumor cells grow. In addition, there are other elements in the tumor microenvironment, such as the matrix, other cells like fibroblasts that can also be usurped by the tumor to make the tumor grow better. We’ve heard a lot about de-convoluting those tumor-associated partner cells and their products. We can now strategically target what is a very bad to microenvironment into one that is much more receptive to immunotherapies.

Arthur Brodsky, PhD 

It is exciting that we’re starting to pair the general immunotherapies that target the T cells with a greater appreciation of the complexity of the tumor microenvironment and breaking frontiers on the therapeutic angle. What progress have we seen recently when it comes to the newer, personalized immunotherapies like cell therapies and vaccines?

Nina Bhardwaj, MD, PhD 

This is a very exciting area. At this year’s meeting, we heard the first results of a neo-antigen vaccine in the setting of melanoma. This vaccine is made from antigens we call neo-antigens.

So what is a neo-antigen? As you can imagine, when tumor cells are growing, they undergo lot of mutations. They do that because of inherent discrepancies in DNA replication, but also to escape the immune system. When that happens, these mutations result in the formation of new proteins that we call neo-antigens because they’re foreign to the immune system.

One of the advantages of neo-antigens is that because they are foreign to the immune system, they can be recognized as highly immunogenic products. We can take advantage of that and formulate them into vaccine products. This year, we head about the formulation of personalized neo-antigens. Remember, each tumor that a patient has is different from the next patient’s tumor. Each patient’s tumor will have its own set of neo-antigens.

In one study, patients who had had a history of melanoma but were tumor free, were given their own personalized neo-antigen vaccines in combination with a checkpoint inhibitor, pembrolizumab. It targets thing the inhibitory molecule PD-1 on T cells. One arm received that combination, the other arm received just the anti-PD-1. The arm that received the vaccine plus the anti-PD-1 had better recurrence free survival rates that were statistically and clinically significant than the other arm that just got the anti-PD-1.

This is the first study of its kind, a randomized study. It was a small study, but nevertheless, very exciting. There will be a follow up phase 3 study. This really put the concept of cancer vaccines on the map. We’re very hopeful that this will translate into long term benefit in the larger upcoming trials. A number of these trials are going to be happening over the next year.

In addition to these neo-antigens, we also have antigens that are shared across patients. Those will be more off-the-shelf type vaccines, which I think will also be part of our future armamentarium against cancer. We also have T cell therapies that have been approved to treat malignancies like multiple myeloma, leukemias, and lymphomas. The challenge really has been how to implement T cell therapies into solid tumors.

We are seeing advances as investigators are learning how to manipulate T cells to make them attack tumor cells better, to grow better, to be sustained better through the expression of molecules that make them last longer, and to be more effective. They are also much more specific.

Arthur Brodsky, PhD 

Obviously, these vaccines and these cell therapies were made possible by technological breakthroughs, so I want to zoom out here. How are technologies helping to advance the field right now, both in terms of helping aid research discoveries, but also enhance existing treatments for patients in the clinic?

Nina Bhardwaj, MD, PhD 

We want to try to prevent cancer from happening initially. When it does happen, we want to catch it in early stages rather than more advanced stages. There are currently efforts to try to screen patients much earlier through genetic testing, and through testing blood. For example, we want to see whether or not there’s evidence through spotting DNA of tumor cells in the blood that might bring the patient to a doctor’s attention much earlier.

We’ve heard about things like Cologuard, which look for blood in the stool, which is used to screen patients who are high risk of developing colon cancer. There are now efforts that are being applied to take a patient’s blood and screening the blood to look for early markers by screening DNA of cancer that might be not openly apparent, but nevertheless detectable through screening procedures.

There are major efforts that are bringing in a number of different kinds of tests to detect cancer early through the screening of blood samples. Along those lines, we have amazing new technologies that are looking at tumor compartments, but also things like urine, blood, cerebrospinal fluid, looking at bacteria in the tumor, bacteria in the gut, and so forth. Through these methods, we are trying to identify other features of the tumor that will give us more information about how to treat or tackle a tumor.

Some of these tests include looking at a tumor three-dimensionally by looking at cellular subtypes, by looking at the DNA and the RNA they make, and getting a lot of information about the nature of the tumor itself. We can learn about what cells are in the tumor, what the tumor signaling to other cells, and what products the tumor is making. These very sophisticated tests can give us really a three-dimensional view of the tumor and helps us as immunologists to understand how the tumor is outwitting the immune system, but also then how we can really manipulate the immune system to treat the tumor. Some of these tools are called Visium, Codex, single cell sequencing, and whole exome sequencing. These terms might be familiar to some in your audience.

Arthur Brodsky, PhD 

I think one of the most promising approaches now that we’re employing is to not treat every cancer the same. To try to understand the nature of each patient’s unique tumor, which could help in diagnosis and help doctors determine what treatment might work best for them. The key is figuring out how each patient is going to respond to a certain treatment.

I know side effects can also be an issue with immunotherapy sometimes. Are these technologies and these approaches helping us to better understand what causes side effects, and who might be most likely to experience them?

Nina Bhardwaj, MD, PhD 

I think your point about trying to understand or predict how patients might respond to treatment is a very important one. Some of the testing that I mentioned will help us determine when to intervene early. It could also explain if there a greater likelihood of how a patient is going to respond and have side effects to immunotherapy.

One example is patients receiving CAR T cell therapies can develop a very highly inflammatory syndrome that is very serious called cytokine release syndrome (CRS). By following biomarkers in the blood, we can intervene very early, and treat those patients with antibodies that neutralize factors that promote this inflammation. That’s one situation where through following a patient’s blood we can actually determine who might be at high risk.

Then there are other biomarkers in the blood that help us predict who might develop graft-versus-host disease (GvHD) in the transplant setting. I think it’s a great time because by analyzing blood cells, blood analytes, protein, and DNA, you can try to preempt the potential side effects of immunotherapies.

Arthur Brodsky, PhD 

Clinical trials are such an important part of the immunotherapy space to help answer these questions that remain unknown, as well as to test new treatments. In terms of improving the efficiency of clinical trials, as well as efforts to improve accessibility of trials and improve health care equity, what initiatives pop out at you that patients should be aware of?

Nina Bhardwaj, MD, PhD 

I think one of the most important that is come out is Cancer Moonshot Initiative that was recently renewed and reignited by President Biden.

We know that depending upon the location and the site, clinical trials can be closed off to many, many patients because of a number of different reasons. It’s important to have health care equity and make trials available to everyone. One is at the community level, ensuring that doctors in the community have awareness and access to trials, and can inform their own patients about what trials are accessible and available in the community or close by the community at bigger medical centers.

The moonshot is trying to develop approaches to include people and patients into these support the trials by making them simpler, reducing exclusion criteria by making more clinical trials available through their clinical trial networks. They can also do extensive research on trying to understand why patients either perceive trials as barriers or that they are not being made aware of trials from which they could benefit from.

In addition, the Cancer Moonshot Initiative is trying to enhance diversity in terms of investigators who are coming in and working on establishing careers, and possibly undertaking trials. These are major initiatives now that are designed to make clinical trials much more available to patients around the country. Telehealth initiatives are also helping us do that. I expect that will also improve accessibility for patients.

Arthur Brodsky, PhD 

Those initiative sounds very promising. As you mentioned, there’s a number of reasons that are preventing certain groups from being able to take advantage of clinical trials. One of them, as you alluded to, is education. Just simply making people aware of it, or, on the other hand, maybe they are aware of them, but have misconceptions about what they’re really about or how they can access them. I think getting the word out will definitely be an important first step to helping to solve some of these issues.

Nina Bhardwaj, MD, PhD 

I think medical centers, and grant-funded institutions in particular, are making major efforts to be more inclusive of patients. In our case with Mount Sinai, we have a very diverse population locally. 40 percent of our trials are comprised of nearby patients who reflect the diversity of the population locally. Those of us who are clinicians that are in such communities also need to be better informed and more inclusive, making these trials available to our patients.

Arthur Brodsky, PhD 

It’s great to hear what these institutions are doing. However, I know an issue for some people who might not live near a major metropolitan city is they don’t have access to these big institutions with trials and efforts to help get them involved. What would you suggest for people who are constrained by geographical barriers?

Nina Bhardwaj, MD, PhD 

I think if you have access to a computer, you can look up CRI’s Clinical Trial Finder and see what trials are available out there. The CRI family does a great job of making that available to community at large. It also updates the community on new approved drugs that are approved by the FDA. It’s probably the most up-to-date database that I’m aware of. I would urge patients to investigate the CRI site for accessibility to clinical trials.

Arthur Brodsky, PhD 

Finally, what are you most excited about for the field of cancer immunotherapy for the last half of 2023?

Nina Bhardwaj, MD, PhD 

I’m very excited about the idea that cancer prevention vaccines can impact patients’ lives and reduce recurrence or prevent cancers from developing. I think that in combination with the number of exciting new therapies already approved, this will be the wave of the future. Also, I’m very excited about cancer prevention approaches, and helping individuals to prevent cancer from taking hold. In the next decade, there will be many new tests that are going to be able to screen patients early and identify patients who are at risk of developing cancers much more efficiently.

Lastly, I’m also very excited about what we call neoadjuvant therapies where usually we were treating patients by either resecting the tumor and then giving chemotherapy or immunotherapy. And now, at least for earlier stage cancers, we’re seeing more evidence to give immunotherapy upfront, even before surgery, in the hope that we can shrink tumors or clear them early on. There’s so many exciting things in the next decade that are going to be truly awesome.

Arthur Brodsky, PhD 

Just to follow up on one of your points: presumably the idea behind treating tumors earlier with immunotherapy is before the tumor has advanced in progress and develop more tricks, the immune system, we would hope, has a better shot of eliminating the tumor at those early stages. Is that accurate?

Nina Bhardwaj, MD, PhD 

Early on, the tumor hasn’t become clever enough to outwit the immune system and bring in all these other factors that we discussed earlier that make it much harder for us to treat cancers. Early detection, early screening, and early treatment are what we want to aim for in our patients. We want to have the whole population at large be much more aware that these initiatives are happening, and that they should take advantage of them. The Cancer Research Institute has really been at the forefront for decades at trying to do this. It’s an exciting time for the field.

Arthur Brodsky, PhD 

Well, that’s all for today. Thank you so much, Dr. Bhardwaj for sharing your expertise and insights with us.

For more of our webinars and the additional resources we have for patients and caregivers as part of CRI’s Answer 2 Cancer educational programs, we encourage you to check out our website at CancerResearch.org/patients.

Here you can read and watch stories shared by patients who have received immunotherapy treatment across a wide variety of cancer types. You can browse our entire library of past webinars and immunotherapy patient summit series featuring the world’s leading immunotherapy experts, like Dr. Bhardwaj. You can access information on other resources, including treatment, emotional support, and financial assistance and get help locating an immunotherapy trial via our CRI Clinical Trial Finder.

And thank all of you for your attention today. I hope you found today’s webinar interesting and informative. And again, you can watch this and all of our other webinars on our website at CancerResearch.org/webinars.

Finally, Dr. Bhardwaj, thank you so much, again for helping to highlight the exciting future of the field, as well as the amazing work that you’re doing to help patients we wish you the best of luck.

Nina Bhardwaj, MD, PhD 

Thank you for having me and wishing our viewership all the very best and lots of good health!