Antibody Dependent Cell-Mediated Cytotoxicity Selection Pressure Induces Diverse Mechanisms of Resistance (scATAC-Seq)

Targeted monoclonal antibody therapy has emerged as a powerful therapeutic strategy for cancer. Unfortunately, only a minority of patients haves durable responses and the development of resistance remains a major clinical obstacle. Antibody-dependent cell-mediated cytotoxicity (ADCC) represents a crucial therapeutic mechanism of action; however few studies have explored ADCC resistance. Using multiple in vitro models of ADCC selection pressure, we have uncovered both shared and distinct resistance mechanisms. We employed CITE sequencing and single-cell ATAC-seqeuncing to interrogate molecular mechanisms of resistance. Overall design: Comparative DNA accessibility analysis of scATACseq data for A431, FaDu, and SKOV3 cell lines, both sensitive to and with acquired resistance to ADCC