"Inhibition of Inhibition: Mechanism of CTLA-4 and PD-1-modulating Antibodies for Oncology"
Senior Vice President, Biologics Discovery Bristol-Myers Squibb
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The immune response to a tumor is a complex, orchestrated network of stimulatory and inhibitory signals. Antibodies that target inhibitory receptors such as CTLA-4 and PD-1 appear to restore cancer patient's endogenous immune responses to their disease. The clinical experience with these antibodies has shaped the immune-oncology pipeline of Bristol-Myers Squibb.
Ipilimumab, an antibody directed against CTLA-4 (cytotoxic t-lymphocyte-associated antigen 4) is now approved for the treatment of metastatic melanoma. Nivolumab, an antibody directed against PD-1 (programmed death-1) is now being tested in multiple phase 3 trials in multiple patient populations, with encouraging results in metastatic melanoma recently published. Preclinical and clinical investigations of the mechanism of action of these drugs will be reviewed. These mechanisms provides guidance for the discovery and development of new agents for the treatment of cancer.
Dr. Lonberg is Senior VP at the Bristol-Myers Squibb Biologics Discovery site in California, where cancer immunotherapy is a major research focus. Dr. Lonberg began his career in industry in the research group at GenPharm International that developed genetically engineered strains of mice with germline-configuration human immunoglobulin genes. These transgenic animals have been used to discover over two dozen clinical-stage human sequence antibodies, including five FDA approved products. In 1997, GenPharm was acquired by Medarex, which was in turn acquired by Bristol-Myers Squibb in 2009.
Dr. Lonberg has published in the areas of molecular biology, developmental biology, immunology, and biotechnology. He is an inventor on numerous issued patents, including the third US patent covering a genetically engineered animal, and on patents covering seven marketed therapeutic drugs. He received his PhD in Biochemistry & Molecular Biology from Harvard University in 1985.