Joshua D. Brody, M.D., CRI Lloyd J. Old STAR Icahn School of Medicine at Mount Sinai

This award will allow us to develop–in the lab and in our patients with incurable cancers–immunotherapies which teach T cells to eliminate tumor cells and to thwart tumors’ evasion of immune attack.
Area of Research: Breast Cancer, Head and Neck Cancer, Leukemia, Lymphoma

As a CRI Lloyd J. Old STAR, Dr. Brody is investigating a therapeutic cancer vaccine approach—known as in situ vaccination, or ISV—that induces anti-tumor immunity at the tumor site and can also cause regression of tumors throughout the body.

In animal models, Dr. Brody has observed that ISV made PD-1 checkpoint immunotherapy—which was normally ineffective in this context—much more beneficial, leading to cures in 75% of cases. Subsequently, he initiated a new trial combining ISV with PD-1 immunotherapy for lymphoma, breast, or head and neck cancer patients. The first patient treated has already shown tumor regression. However, even when ISV successfully elicits an anti-cancer immune response, sometimes tumors can escape by ‘losing’ the markers, or antigens, that the immune system was targeting. Fortunately, Dr. Brody has discovered that the Fas gene can make tumor cells sensitive to immune cell killing even if they’ve lost the target antigen, as long as they are near cells that express it. 

Overall, Dr. Brody’s work will focus on two goals: to characterize and hopefully improve ISV’s anti-tumor immune activity and to further potentiate Fas-mediated bystander killing of cancer cells to prevent antigen escape.

Projects and Grants

Cross-Priming Anti-Tumor T Cells with In Situ Vaccination and Potentiating Bystander Killing

Icahn School of Medicine at Mount Sinai | Breast Cancer, Head and Neck Cancer, Leukemia, Lymphoma | 2020

Flt3L-primed in situ vaccination for low-grade lymphoma

Icahn School of Medicine at Mount Sinai | Breast Cancer, Lymphoma, Melanoma, Prostate Cancer | 2015

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