Bispecific Antibodies to PD-1 and CTLA4: Doubling Down on T Cells to Decouple Efficacy from Toxicity

Summary: Although combination anti–PD-1 and anti-CTLA4 mAbs have revolutionized outcomes for many cancers, their utility has been limited due to significant immune-related toxicities and the emergence of resistance. In this issue of Cancer Discovery, Dovedi and colleagues describe the development and preclinical testing of MEDI5752, a bispecific anti–PD-1/CTLA4 antibody designed to optimize therapeutic response by maximizing CTLA4 blockade on antigen-experienced T cells, thereby increasing efficacy and potentially minimizing toxicity. See related article by Dovedi et al., p. 1100.