Jianyong Wang | Senior Principal Scientist
Genentech
Dr. Wang is currently a senior principal scientist at Genentech (Roche) with more than eighteen years of working experience in antibody biologics. His responsibilities include developing and implementing discovery strategies for antibody-based biologic drugs, driving and evolving antibody molecules from the earliest screening efforts to the characterization of the final clinical drug. He is also interested in developing and adapting innovative technology platforms to suit discovery of the next generation of biologic drug modalities. Dr. Wang's recent research aims to understand macrophage functions in different health conditions, in order to develop novel drugs that modulate their activities in diseases and improve clinical outcomes.
Appearances:
Festival of Biologics Day 1 @ 15:40
Therapeutic Antibodies: Rewiring Macrophages in the Tumor Microenvironment
As one of the most abundant immune cells in solid tumors, tumor-associated macrophages (TAMs) are characterized as high plasticity with both pro- and anti-tumor functions, depending on the microenvironment. On one hand, TAMs are capable of engulfing dying tumor cells, leading to the clearance of associated tumor antigens, which helps the tumor to escape the host immune surveillance. TAMs also secret immune-suppressive cytokines that maintain a pro-tumor microenvironment. Consequently, TAMs contribute to the resistance of checkpoint inhibitors, chemo/radio-therapeutic agents, and adoptive T cell immunotherapies in clinic. Alternatively, when TAMs are properly activated, they destroy live cancer cells or other immunosuppressive cells, acting as a defensive mechanism against tumors by killing them directly and indirectly. Thus, modulation of TAMs functions represents an attractive approach for cancer immunotherapy. Here, we share two case studies to exemplify that antibody drugs enhance cancer immunotherapy by modulating macrophage functions. First, we established a real-time, live cell imaging-based phagocytosis method that is fully automated with high throughput capability and less disturbance to macrophages. By using our established phagocytosis assay, we discovered potent anti-MerTK monoclonal antibodies (mAbs) that inhibit macrophage-mediated phagocytosis of apoptotic cancer cells both in vitro and in vivo. Dosing of anti-MerTK mAbs in a syngeneic mouse tumor model resulted in robust anti-tumor responses when combined with the checkpoint inhibitors anti-PD1/PD-L1. Leveraging our advanced imaged-based antibody-dependent cellular phagocytosis (ADCP) assay, we discovered a novel mAb with enhanced ADCP mediated by macrophages. This mAb uniquely targets and efficiently depletes tumor-infiltrating regulatory T (Treg) cells, a critical population of immune-suppressive cells in the tumor microenvironment. This constitutes another promising strategy for targeting the immunosuppressive tumor microenvironment. Besides drug discovery, our established imaged-based phagocytosis methods have broad applicability to dissect the kinetics and molecular mechanisms of cellular phagocytosis.
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