Characterization of a humanized PD-L1 blocking antibody with pH-dependent antigen binding in a humanized syngenic tumor model.

81Background: Checkpoint inhibition is a promising approach for cancer treatment with durable responses and survival benefits. Currently, immune-checkpoint inhibitors are delivered at maximally tolerated doses, resulting in significant toxicities and cost burden. There is significant need to develop more efficacious and safer immune checkpoint inhibitor. Towards this goal, we have developed a next-generation humanized PD-L1 antibody with pH-dependent antigen binding and evaluated its biological activities in vitro and in vivo. Methods: Hybridoma approach was employed to generate anti-PD-L1 antibodies. A cell-based receptor-ligand blocking assay was employed to identify neutralizing antibodies. Antibodies with pH-dependent antigen binding property were identified and characterized further with those without using PD-L1/PD-1 binding assay, mixed lymphocyte reaction assay, and in vivo tumor growth inhibition assay in syngeneic MC38 tumor model expressing human PD-L1 protein. Results: A panel of neutralizing ...