PD?1?specific “Blocking” antibodies that deplete PD?1 ⁺ T cells present an inconvenient variable in preclinical immunotherapy experiments

Therapeutic antibodies blocking PD-1-/PD-L1 interaction have achieved remarkable clinical success in cancer. In addition to a target molecule, some isotypes of can activate complement, NK cells or phagocytes, resulting death the cell expressing antibody's target. Human anti-PD-1 therapeutics use antibody designed minimize such antibody-dependent lysis. contrast, reagents used mice are derived from multiple species, with different isotypes, and not engineered reduce death: few studies analyze discuss how species isotype may impact data interpretation. We demonstrate here that therapy promote activation proliferation murine PD-1-expressing CD8 T sometimes led instead loss antigen specific cells. This phenomenon was seen two tumor models model virus infection, varied clone antibody. Additionally, we compared competition among clones find combination allows detection despite presence anti-PD1 vivo. These bring attention possibility unintended depletion commonly anti-mouse PD-1 clones, should provide valuable resource for design interpretation mice.