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Programmed cell death protein 1 (PD-1) is currently the most widely exploited checkpoint blockade target. PD-1 is induced on T cells following activation and inhibits the signals of the T cell receptor and costimulatory molecules such as CD28,slowing an ongoing effector immune response to prevent immune-mediated damage. Checkpoint blockade immunotherapy of cancer seeks to prevent these inhibitory signals from slowing the immune response, reinvigorating effector T cell activity, and promoting tumor cell killing. Anti-PD-1 monoclonal antibodies (mAbs) have achieved widespread clinical success, but the relationship between binding affinity and functional efficacy of clinical anti-PD-1 antibodies is unpredictable.