Avelumab induces superior Fc-Fc receptor-dependent natural killer cell stimulation and dendritic cell cross-talk compared to durvalumab

Natural killer cells and dendritic cells are instrumental in controlling cancer. However, the impact of PD-L1 blockade therapy on these immune cell types is not well understood. Furthermore, across many clinical trials, different anti-PD-L1 antibodies have produced varying levels of efficacy in patients, and the basis of these differences are obscure. Avelumab, a native Fc IgG1 antibody, and durvalumab, a mutant-Fc IgG1 antibody, are two of the most commonly used anti-PD-L1 agents for cancer immunotherapy. We compared the mechanistic effects of these agents. Our study shows the robust impact of Fc-signaling on NK cells by avelumab. In contrast, durvalumab failed to induce NK cell activation or promote NK-DC cross-talk.