William Hahn, MD, PhD
Executive Vice President and Chief Operating and Transformation Officer, Dana-Farber
William Rosenberg Professor of Medicine, Harvard Medical School
Antibodies that target specific tumor-expressed antigens are now the standard of care for some cancers. However, the identification of new proteins that are differentially expressed on tumors and are amenable to antibody binding remains challenging. To address this bottleneck in developing new antibody-based drugs for solid tumors, a team led by Prof. William Hahn, MD, PhD, executive vice president and chief operating officer at Dana-Farber, and Bärbel Schröfelbauer, PhD, lead scientist, Cancer Surface Profiling, developed the PhAST (Phenotypic Antibody and Simultaneous Target)-discovery platform, for the high-throughput, unbiased, simultaneous discovery of therapeutic antibodies and their targets.
“The PhAST platform integrates much of what researchers have learned in the past 40 years of therapeutic antibody development and combines it into an integrated way of finding antigens and antibodies at the same time,” says Dr. Hahn. It allows for the unbiased discovery of hundreds of antibody/target pairs selective for any cancer type of interest through a single round of screening. Instead of many months to discover antibodies against a single target, the PhAST platform allows for the discovery of many targets and antibodies in parallel, shortening the previously lengthy process to two to three months.
The PhAST platform has led to the discovery of various new targets in ovarian cancer, which, at stage IV, has a five-year survival rate of only 30.8%.
Among these targets is BCAM, a protein that is highly expressed on the surface of high-grade serous ovarian cancer cells and has been shown to be involved in adhesion and migration of carcinoma cells.
In parallel to BCAM, a PhAST screen identified 37 fully human antibodies targeting it. With Accelerator funding, the research team is expediting the development of some of these novel antibodies, by enabling in vivo studies, a critical step towards translating the technology to humans.
Other contributors to the project include Prof Sarah Hill, MD, PhD, physician scientist in the Department of Medical Oncology and Division of Molecular and Cellular Oncology and Prafulla Gokhale, PhD, director, Experimental Therapeutics Core at Dana-Farber.
The PhAST platform integrates much of what researchers have learned in the past 40 years of therapeutic antibody development
William Hahn, MD, PhD
Team Members
Bärbel Schröfelbauer, PhD
PhAST Team Leader, Dana-Farber
