T cell modulation: Anti-PD-1 antibodies for the treatment of cancer

Abstract

The expression of inhibitory receptors on tumor specifi c T cells leads to compromised effector function such as decreased proliferation, cytokine secretion, and tumor cell lysis. These receptors can be targeted therapeutically using monoclonal antibodies, an approach that was termed “checkpoint blockade”. The improved survival of advanced melanoma patients treated with the anti-CTLA-4 antibody ipilimumab validates this new treatment concept. Inhibition of another inhibitory pathway, PD-1/PD-L1, using monoclonal antibodies has recently shown much promise in the treatment of melanoma, renal cell cancer, non-small cell lung cancer, among other tumor types. Durable anti-tumor activity with a favorable safety profi le has lead to fast paced clinical development of many compounds targeting both PD-1 and PD-L1.