Immune checkpoint inhibitors targeting programmed cell death-1 (PD-1) in cancer therapy

Immune checkpoint inhibitors, especially anti-programmed cell death-1 (PD-1) antibodies, have revolutionized cancer therapy. A PD-1 antibody, nivolumab, was the first of these agents to be approved by the Pharmaceuticals and Medical Devices Agency (PMDA) of Japan, as a new cancer drug for melanoma, in July 2014. While PD-1 mAb therapy has so far been approved only for untreated malignant melanomas and non-small cell lung cancer, many clinical studies on various types of cancer have been conducted worldwide. Immune checkpoint inhibitors target lymphocytes rather than cancer cells, and evoke an anti-tumor immune reaction. Since the activated lymphocytes recognize various tumor-associated antigens including a mutated antigen, immune checkpoint inhibitors exhibit continuous long-term effectiveness, despite the generation of genetic mutations in cancer cells. As compared with previous cancer treatments, immune checkpoint inhibitors show superior efficacy against tumors with fewer side effects. Therefore, these novel immune checkpoint inhibitor agents are anticipated to become a 4^th cancer treatment option following surgery, chemotherapy, and radiation therapy. Herein, we review the main clinical results of PD-1 mAb cancer immunotherapy obtained to date and discuss issues relevant to administering this form of treatment.