Anti-PD-1 and Anti-B7-H1/PD-L1 monoclonal antibodies

Tumors can evade immune recognition by usurping regulatory pathways which, under normal circumstances, down-modulate immune activation and maintain tolerance to self. A key pathway operational in cancer-induced tolerance is composed of programmed death-1 (PD-1, CD279), a receptor expressed on activated T and B cells, and its ligands B7-H1/PD-L1 (hereafter B7-H1, CD274) and B7-DC/PD-L2 (hereafter B7-DC, CD273). PD-1 bears homology to CTLA-4 but transmits distinct inhibitory signals. B7-H1, which is homologous to other B7 family members, is constitutively expressed by many human cancers and is thought to be the major inhibitory ligand for PD-1; it is also expressed on activated hematopoietic cells, vascular endothelial cells, and cells inhabiting inflammatory microenvironments. Based on animal models implicating the importance of the B7-H1/PD-1 pathway in cancer-induced immunosuppression, and human studies correlating tumor expression of B7-H1 with unfavorable clinical outcomes, interest has recently focused on exploring B7-H1/PD-1 blockade as a new approach to cancer immunotherapy. Early results from clinical trials suggest that this may be an effective strategy for treating patients with advanced metastatic melanoma as well as malignancies of epithelial origin.