Associate Attending Biologist
Memorial Sloan Kettering Cancer Center
New York, New York
Areas of Focus: Treatment and Tumor Biology
Co-Investigator: Jedd Wolchok, MD, PhD, Memorial Sloan Kettering Cancer Center, New York, New York
- Seeking strategies to optimize an anti-tumor immune response in breast cancer patients.
- Several approaches to improve immunotherapy are being pursued, including a phase I clinical trial for a vaccine in HER2-positive metastatic breast cancer.
- These efforts could have a significant impact on advancing immunotherapy to benefit breast cancer patients.
The hope for a breast cancer vaccine is hampered by the fact that breast cancer cells look too much like normal cells and escape immune surveillance. Drs. Merghoub, Wolchok and Norton have devised a novel vaccine that overcomes this barrier. The vaccine is currently in clinical trial for patients with metastatic breast cancer. Other efforts are ongoing to improve response to immunotherapies.
Full Research Summary
Targeted immunotherapy has re-emerged as an exciting therapeutic option in the arsenal against cancer. Clinical trials of immunotherapy drugs in breast and other cancers have demonstrated a sustained clinical benefit for some patients, but challenges persist in understanding the best approach for each patient and in improving the response to immune-based therapies.
Effective immunization against breast cancer is difficult because breast cancer arises from cells that were once normal, and our bodies have elaborate controls to stop the immune system from attacking our own tissues. Drs. Merghoub, Wolchok and Norton have found a way to trick the immune system by using a vaccine from a different species. It works because the immune system recognizes the vaccine as “foreign” and generates an immune response to destroy breast cancer cells as if they were foreign invaders.
A Phase I clinical trial to test the vaccine for safety and efficacy in patients with HER2-positive metastatic breast cancer is ongoing (ClinicalTrials.gov NCT00393783). The research team will continue to evaluate the biomarkers of response in patients and begin along with several other ongoing efforts including studies to optimize the combination of immunotherapy with radiation therapy and to evaluate a combination approach to improve response to immunotherapy.
Two mechanisms by which tumors can escape the immune system is by promoting local immune suppression and by changing their metabolism. The Memorial Sloan Kettering team is working on two potential drugs that target these activities and will test them in combination with immune therapies in laboratory models. They expect this dual approach to inform the design of future clinical trials and advance the use of immunotherapy for breast cancer patients.
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.