Elucidating the role of human anti-PD-L1 antibodies Fc-dependent signaling in tumor therapy

Checkpoint inhibitor immunotherapies (checkpoint blocking antibodies) have helped many, but unfortunately, not all patients overcome advanced cancer. To help the remaining patients, we need a better understanding of how these therapeutic antibodies work and what aids their effectiveness. Our proposed study aims to do just that, by focusing on the modes of action of anti-PD-L1 checkpoint blocking antibodies. We have recently found that while the “active ends” of these drugs target the pro-tumor PD-1 pathway, their “back ends” also improve their effectiveness. Driven by this observation made for mouse antibodies, here we will advance our study to focus on the impact of the “back ends” of human anti-PD-L1 drugs. We will use advanced mouse genetic, microscopy, and molecular biology approaches to decipher the therapeutic mechanism mediated by of the “back ends” of these immunotherapies. This study may pave the way for the development of new ways of designing anti-PD-L1 checkpoint blocking antibodies to further improve their anti-cancer activity.