Lay summary
Immunotherapies for cancer treatment, particularly monoclonal antibodies, are pivotal in enhancing immune cell recognition and destruction of cancer cells. Avelumab, an anti-PD-L1 monoclonal antibody, prevents the immunosuppressive interaction between PD-L1 and PD-1 and enables tumor cell destruction via antibody-dependent cell cytotoxicity (ADCC). However, the Avelumab Fc domain is not fully optimised for ADCC by human natural killer (NK) cells. This study aims to engineer Avelumab with mutations to increase its ability to kill breast cancer cells. The hypothesis is that the re-engineered Avelumab will block the PD1/PD-L1 axis as well as exhibit enhanced ADCC activity through increased NK cell activation. The primary research question is whether Fc region mutations in Avelumab enhance its cytotoxic effect on breast cancer.