Jedd Wolchok

Jedd Wolchok, MD, PhD is the Meyer Director of the Sandra and Edward Meyer Cancer Center at Weill Cornell Medicine and a Professor of Medicine. He is one of the founders of modern cancer immunotherapy, best known for pioneering ipilimumab (anti-CTLA-4) clinical development and the concept of immune-related adverse events management. In recent years, he has become a leading investigator of resistance mechanisms to both checkpoint immunotherapy and CAR-T cell therapy in solid tumors. His group has performed extensive correlative studies in melanoma patients receiving combination nivolumab plus ipilimumab, defining the genomic and immunological features associated with durable complete responses versus primary or acquired resistance. His translational work has characterized the multiple resistance barriers facing CAR-T cell therapy in solid tumors, including antigen escape through downregulation of target antigen expression, T cell exhaustion driven by tonic CAR signaling and chronic antigen stimulation in the hostile TME, and physical exclusion by desmoplastic stroma. Dr. Wolchok leads clinical trials of next-generation CAR-T constructs engineered with armoring strategies (IL-15, dominant-negative TGF-betaR) to overcome exhaustion and stromal barriers in melanoma and other solid tumors.