Investigation of antibody dependent cellular cytotoxicity as a mechanism of action for a novel anti-PD-L1 monoclonal antibody

Purpose Expression of the immune checkpoint protein PD-L1 constitutes a major mechanism of tumor immune evasion. Multiple clinical trials in solid tumors have demonstrated that inhibition of tumor PD-L1 or immune effector PD-1 via monoclonal antibodies (mAbs) can produce dramatic clinical responses in many cancer patients. The main function of these mAbs is to inhibit signaling induced by ligation of PD-L1 on tumor cells with PD-1 on tumor infiltrating immune effectors. Antibody-dependent cellular cytotoxicity (ADCC) represents an additional mechanism of action for mAbs of the IgG1 isotype. In the current study, we describe investigations of a novel anti-PD-L1 mAb of the IgG1 isotype (MSB0010718). This mAb is currently in Phase I clinical trials for patients with metastatic or locally advanced solid tumors at the NCI, and is the first such mAb with the capacity to induce ADCC of PD-L1 positive tumor cells. We sought to investigate MSB0010718’s ability to induce ADCC and to determine factors affecting tumor cell sensitivity to this mechanism. Results