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CRI Advisory Council Member Receives Endowed Professorship

October 18, 2013 | Matthew Tontonoz

CRI Scientific Advisory Council member Nina Bhardwaj has been awarded an endowed professorship at Mount Sinai School of Medicine. Named after philanthropist Ruth Ward Coleman, the professorship is one of 6 such positions being awarded to distinguished clinician-scientists at Mount Sinai in a variety of disciplines. 

Nina BhardwajFormerly a professor of medicine at NYU, Bhardwaj was hired by Mount Sinai in 2013 to direct their immunotherapy program, including a new state-of-the-art vaccine facility under construction. Bhardwaj is known for her pioneering work on dendritic cell-based vaccines, which will continue to be a focus of the Mount Sinai program.

“Our strength is looking at innate immunity and how it's usurped in cancer,” says Bhardwaj. “We want to understand how to use innate immune cells to reverse immunosuppression in the tumor microenvironment.”

The cancers they hope to treat with immunotherapy include melanoma, head and neck, liver, lung, and breast.

From Autoimmunity to Cancer

When Bhardwaj was a postdoc in Ralph Steinman’s lab at Rockefeller University in the 1980s, she was interested in autoimmunity—the damaging process that occurs when one’s immune system turns against one’s own body. She received funding from the CRI Irvington Posdoctoral Fellowship Program in 1984 to study the immune response in rheumatoid arthritis, a condition that results from chronic inflammation of the joints. At the time, she says, much less was known about the immune response to cancer. But Bhardwaj was intrigued by a fascinating question: why was the immune system so tolerant of cancer cells when it could attack one’s body so viciously? She ultimately switched the focus of her research from autoimmunity to cancer, but still with the goal of unlocking the secrets of the immune system.

"I thought it would be fascinating to learn that side of it as well," she says.

In the late 1990s, Bhardwaj began work aimed at developing cancer vaccines. She focused on dendritic cell vaccines because these were the cells that she, Steinman, and colleagues had discovered were particularly good antigen-presenting cells. When the CRI/Ludwig Cancer Vaccine Collaborative got up and running in 2001, Bhardwaj headed a number of such cooperative trials.

Currently, one FDA-approved dendritic cell vaccine exists: Provenge, for prostate cancer. But Bhardwaj is interested in developing others.

At this point, what they’re doing is mostly proof-of-principle research. "We're trying to understand how these cells can actually function to prime immunity," says Bhardwaj. Many variables still need to be addressed. "The formulation of the antigen, the adjuvant, the delivery approach—all of those things are still being considered."

Between Bench and Clinic

Dr. Bhardwaj received both her M.D. and Ph.D. from NYU. As a clinician-scientist, Bhardwaj is interested in conducting scientific research at the interface between basic science and clinical applications. 

Bhardwaj is the recipient of a Clinical and Laboratory Integration Program (CLIP) grant from CRI, awarded in 2013. The research she is being funded to conduct—on an enzyme called MMP-2—came out of her clinical work on vaccine trials, she says. 

One of the fellows in her lab, Emmanuelle Godefroy, discovered that some of T cells present in patients’ melanoma tumors recognized MMP-2 as an antigen. They went on to discover that this enzyme gets processed and presented by dendritic cells in a way that wreaks havoc with the immune response.

"We essentially identified this cell antigen that could skew immunity in the wrong way," says Bhardwaj. "Now we're trying to understand how that happens, and and by doing so to identify mechanisms that might be used to block that effect.”

Asked why so much recent work in immunotherapy is geared toward melanoma, Bhardwaj says that it’s because some of the earliest work on tumor antigens was done in melanoma. "It sort of became the model cancer," she says. But researchers now know that many other tumors are immunogenic as well, and can be targeted with immunotherapy. Even lung cancer can induce an immune response, she notes.

Like many researchers in the field of immunotherapy, Bhardwaj is interested in combining cancer vaccines with other novel approaches, including ones already in the clinic, such as checkpoint blockade antibodies. 

"We’re hoping to develop multipronged approaches," she says.

Dr. Bhardwaj is excited about her new position, and honored to have been awarded the Ward-Coleman professorship. "Mount Sinai is an extraordinary group of individuals who are very interested in immunotherapy," she says. "It's going be a lot of fun to work with them."

Photo: A lymphocyte (pink) scans a dendritic cell (green) for foreign and cancer antigens. Credit: Olivier Schwartz and the Electron Microscopy Core Facility, Institut Pasteur

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