Antidrug Antibodies and Drug Development: Challenges in the Immunotherapy Era

Novel antibody formats such as bispecifics have increased risk of immunogenicity, impacting safety and efficacy. LY3415244, a novel T-cell immunoglobulin and mucin-domain-containing molecule-3 (TIM3)-PDL1 (programmed death (ligand) 1) bispecific caused neutralizing antibody–drug antibodies (ADA) in 12 of 12 patients and required study termination. Novel approaches are needed to ameliorate and manage this undesirable effect of therapeutic antibodies. See related article by Hellmann et al., p. 2773