Several anti-PD-1/PD-L1 monoclonal antibodies (mAb) are currently providing 
evidence of clinical benefit in subsets of cancer patients. The mode of action 
of these mAbs is to inhibit PD-1 on immune cells interacting with PD-L1 on tumor 
cells. These mAbs are either designed or engineered to eliminate 
antibody-dependent cell-mediated cytotoxicity (ADCC), which, however, has been 
implicated as an important mechanism in several highly effective mAb-mediated 
cancer therapies. A fully human anti-PD-L1 mAb would potentially be able to 
block PD-1/PD-L1 interactions and also mediate the ADCC lysis of tumor cells. 
MSB0010718C (designated avelumab) is a fully human IgG1 anti-PD-L1 mAb. The 
studies reported here demonstrate (i) the ability of avelumab to lyse a range of 
human tumor cells in the presence of PBMC or NK effectors; (ii) IFNγ can enhance 
tumor cell PD-L1 expression and, in some cases, enhance ADCC tumor cell lysis; 
(iii) purified NK cells are potent effectors for avelumab; (iv) similar levels 
of avelumab-mediated ADCC lysis of tumor cells are seen using purified NK as 
effectors from either healthy donors or cancer patients; (v) very low levels of 
avelumab-mediated lysis are seen using whole PBMCs as targets; this finding 
complements results seen in analyses of PBMC subsets of patients receiving 
avelumab; and (vi) the addition of IL12 to NK cells greatly enhances 
avelumab-mediated ADCC. These studies thus provide an additional mode of action 
for an anti-PD-L1 mAb and support the rationale for further studies to enhance 
avelumab-mediated ADCC activity.