Titles and Affiliations
Memorial Sloan Kettering Cancer Center
New York, New York
Areas of Focus
- Tumor Biology
Jedd Wolchok, MD, PhD, Memorial Sloan Kettering Cancer Center, New York, New York
Improving response to immunotherapy in breast cancer patients.
Immunotherapy is a treatment strategy that utilizes the body’s immune defenses to fight off disease. A class of immunotherapies called checkpoint inhibitors have been effective in patients with melanoma, lung, and other cancers, but has not been very effective for most breast cancers. The BCRF-supported research of Drs. Merghoub and Wolchok focuses on both developing new immune-based strategies and improving response to existing immunotherapies in breast cancer.
Progress Thus Far
In tumors, both cancer cells and immune cells compete for glucose Drs. Merghoub and Wolchok discovered that by reducing the cancer cell glucose consumption they can increase the ability of anti-tumor immune cells to respond to immunotherapy. The team also demonstrated that tumor destruction with local radiotherapy can strengthen anti-tumor immunity when combined with an antibody that blocks a molecule important for protecting cells from death.
Drs. Merghoub and Wolchok are working on three classes of potential drugs: a drug that blocks immune-suppressive cells called T regulatory cells, drugs that block suppressive cells in a pathway called AHR, and a drug that affects tumor metabolism within the tumor microenvironment. The team will continue to evaluate these drugs and how they function when combined with current immunotherapies in pre-clinical models. The team hopes that because these drugs inhibit both immune-suppressive cells and modulate glucose metabolism, their findings will inform the design of future clinical trials with these agents.
Dr. Merghoub received his BA degree from University of Algiers, Algeria, and MS and PhD degrees with highest distinction from University of Paris, France. His thesis work focused on the study of genetic polymorphism in fetal hemoglobin gene in patients with sickle cell anemia and thalassemia. His findings provided insight to the correlation of genotypes and phenotypes in sickle cell anemia and thalassemia. After graduation, he pursued his postdoctoral research with Dr. Pier Paolo Pandolfi at MSKCC. He characterized the transcriptional properties of the Pokemon gene and its role during development. He also played an active role in the generation of laboratory models for acute promyelocytic leukemia, and furthered his knowledge and experience in genetics. Dr. Merghoub is a Senior Research Scientist in Dr. Wolchok’s lab and an associate lab member in the melanoma and immunotherapeutic service. His research projects investigate the pathogenesis and treatment of melanoma, and in part are directed at developing tools to study melanoma. These projects are heavily collaborative in nature, within the Wolchok lab and across different disciplines at MSKCC. Dr. Merghoub has been co-directing the scientific focus of the Wolchok lab.