David J Zahavi, Rossin Erbe, Yong-Wei Zhang, Theresa Guo, Zoe X Malchiodi, Rachael Maynard, Alexander Lekan, Rosa Gallagher, Julia Wulfkuhle, Emanuel Petricoin, Sandra A Jablonski, Elana J Fertig, Louis M Weiner
Targeted monoclonal antibody therapy has emerged as a powerful therapeutic strategy for cancer. However, only a minority of patients have 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. Persistent ADCC selection pressure yielded ADCC-resistant cells that are characterized by a loss of NK cell conjugation and this shared resistance phenotype is associated with cell-line dependent modulation of cell surface proteins that contribute to immune synapse formation and NK cell function...
December 31, 2023: Cancer Biology & Therapy