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Nina Bhardwaj, MD, Discusses her Cancer Vaccine Research with MSIP

Meet Nina Bhardwaj, MD, PhD, Professor of Medicine (Hematology and Medical Oncology) and Urology, and Medical Director of the Vaccine and Cell Therapy Laboratory (VCTL) at the Icahn School of Medicine at Mount Sinai. Dr. Bhardwaj and her team are conducting groundbreaking research into cancer vaccines, aiming to address a significant patient need on a global scale. MSIP spoke with Dr. Bhardwaj to learn more about her life and education and her team’s cancer research, including its fascinating connection to Mount Sinai’s SARS-CoV-2 vaccine research.

Q: Can you describe your education and professional background? What inspired you to get into cancer immunology and join Mount Sinai?

After graduating from Wellesley College in 1975, I received my MD / PhD degree from the New York University (NYU) School of Medicine (now known as NYU Langone) in 1981; that’s where I got into immunology. NYU’s medical program attracted a lot of immunologists, and once I started working with pioneers in the field, I was hooked. There were so many unknowns regarding how the immune system responds to infections, cancer, and other conditions, and I wanted to understand how the immune system was rendered dysregulated in these conditions. Later, I went to Rockefeller University to work with a team of fellow pioneers in dendritic biology, under the tutelage of Dr. Ralph Steinman, who received the Nobel Prize in Physiology or Medicine in 2011. Antigens notify the immune system to the presence of infection via dendritic cells which prepare the immune response. This is where it became clear that the immune system was critical for attacking viruses, such as influenza and HIV.

I found cancer immunology to be an underappreciated field. I began asking: how could we use the native immune system to combat cancer? I was recruited by Dr. Steven J. Burakoff, the Lillian and Henry Stratton Professor of Medicine and former Director of the Tisch Cancer Institute (TCI) in 2013 to develop a cancer immunotherapy center (now known as the VCTL) and build cancer vaccine platforms. There were many opportunities to understand how cancer worked, and it became an obligation to me to contribute to research efforts in a substantial way and to the best of my ability. That’s what keeps me going: the excitement of discovery, and the new pathways and approaches that can potentially treat cancer.

Q: In your opinion, why has this research field become so prominent across industries and society in general?

Cancer is the #1 cause of mortality in the U.S. and other countries. We can almost look at cancer as an epidemic, with its vast number of patients, the burden on healthcare systems, costs, and many other factors. However, we are creating incredible inroads to target cancer pathways, and this has revolutionized the field. Innovation, combined with patient need and research, has propelled the field tremendously.

Q: Can you describe your current technology / research? What is the status of the personalized cancer vaccine and what are the next steps?  

At the VCTL, we’ve generated a platform that allows us to take a patient’s tumor, sequence it, identify mutations, then predict the neo-antigen that we can formulate into a vaccine. Cancer undergoes mutations all the time, and when this happens, new proteins are formed. We call those neo-antigens because they’ve never been seen by the immune system. We’ve seen several patients who are living longer lives following the use of the platform for a variety of cancer types: bladder cancer, glioblastoma (brain tumor), and more.

Currently, we are thinking about ‘off the shelf’, or shared, vaccines: taking shared mutations, predicting neo-antigens, and using the same vaccine for patients. There are many benefits to the shared vaccine, as personalized vaccines are very expensive and the ‘off the shelf’ version could be manufactured inexpensively. As we think more about shared vaccines in different types of cancer, we see that pancreatic cancer patients, for example, have shared mutations, as do other cancers such as colorectal cancer. This goes to show that there are a lot of opportunities in this space; I’d certainly like to place the shared vaccines into the clinic, for early-stage or preventative settings, as a next step.

Q: In what ways do you collaborate with other experts across Mount Sinai? How would you describe your connection to CastleVax, a Mount Sinai startup company launched in response to the COVID-19 pandemic?

I started working with the Department of Microbiology, particularly Drs. Peter Palese, Adolfo García-Sastre, and Florian Krammer due to the urgency of the pandemic. The team wanted to work with the VCTL to test the immunogenicity (the ability to provoke an immune response) of novel COVID Spike protein variants. These proteins serve as the basis for the Newcastle disease virus (NDV) vaccine platform, which helped to launch CastleVax in 2022. My team at the VCTL continues to have a strong relationship with Microbiology in this respect, as they create the variants and the VCTL helps to establish viability and functionality via viral seed stocks. We currently have a clinical trial at Mount Sinai for the NDV platform, and as new COVID variants appear, we are continuing to develop those seed stocks for global clinical trials. We are delighted to work with them, especially on research that has had such a major, global impact.

As for the NDV vaccine platform’s relationship to the cancer vaccine, I’m hopeful that, since the NDV platform is proving to serve as an effective vaccine against SARS-CoV-2 and its variants, that we can use it to express tumor antigens to make it more amenable to the immune system. I’m asking questions such as: can we express a cancer antigen in place of a Spike protein? Can we use the same platform but switch things around a bit, by adding immune modulators?

The NDV platform that led to CastleVax is an amazing success story of bench-to-bedside efforts. I’m hopeful the cancer platform will turn out to be as well.

Q: How would you describe your relationship with MSIP?

My work with MSIP has certainly picked up substantially over the years, and I’m glad to say we have an excellent working relationship. While we worked together on various agreements in the past, our current focus has been on patent applications related to my team’s work on the cancer vaccine platform. We’ve recently executed a license with a new immunotherapy startup company, Cell BioEngines, focused on cell therapy as ‘drugs’ to treat cancer. I’m very excited about our future endeavors with MSIP; the department has been very supportive and it’s great to work with a group that is equally excited about these approaches to cancer treatment.

Q: What has your experience been like as a female innovator?

I grew up in Kenya, and when I came to the U.S., I worked very hard and was lucky enough to have supportive mentors along the way. Finding great leadership from individuals who had a similar vision inspired me to enter the cancer immunology field. Ultimately, it gave me a lot of freedom to find the right path for research, which was an incredible opportunity that helped me overcome many of the stigmas faced by women in science. As women, we often don’t realize the inherent biases we’re faced with regularly. It’s so important to call them out, to stand up, and to find leaders and colleagues who will listen to you. I’m very fortunate to have colleagues such as Dr. Burakoff, as well as Dr. Ramon Parsons, Director of the TCI, who not only support me, but my team in pursuing research and innovation.

Q: What advice would you give to other female innovators?

You have to find what you love working on. If it doesn’t excite you, I don’t know why you’d be in the field. That’s the best advice I could give. When you find what you’re most passionate about, you will realize there’s so much more to discover. Finding what’s right for you, that’s the way to go.  It may take a while with numerous speed bumps along the way, but the journey is the reward, isn’t it?