-Review-

Development of Cancer Immunotherapy Targeting the PD-1 Pathway

Naomi Kamimura, Alexander M. Wolf and Yoshiko Iwai

Department of Biochemistry and Cell Biology, Institute for Advanced Medical Sciences, Graduate School of Medicine, Nippon Medical School, Kanagawa, Japan

Immune checkpoint inhibitors are causing a paradigm shift in cancer treatment. Immune checkpoint molecules such as programmed cell death protein 1 (PD-1) and cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) dampen T cell activation to avoid autoimmunity and the destructive effects of an excessive inflammatory response. Immune checkpoint signaling can be exploited by tumors to escape host immune surveillance, and immune checkpoint inhibitors enhance antitumor immunity by releasing the brakes on the immune system. PD-1 was identified in 1992 by Honjo and colleagues at Kyoto University. Studies in animal models revealed that PD-1 blockade can inhibit tumorigenesis and tumor metastasis. In addition, PD-1 blockade showed fewer adverse effects than CTLA-4 blockade. Based on these findings, a humanized monoclonal antibody against human PD-1 called nivolumab was developed. Since PD-1 blockade targets lymphocytes rather than tumor cells, the therapeutic effects last longer, even if mutations occur during tumorigenesis. Furthermore, because it does not depend on specific tumor antigens, PD-1 blockade can be applied to various kinds of tumors.

J Nippon Med Sch 2019; 86: 10-14

Keywords
cancer immunotherapy, immune checkpoint inhibitor, PD-1, PD-L1, nivolumab

Correspondence to
Yoshiko Iwai, Department of Biochemistry and Cell Biology, Institute for Advanced Medical Sciences, Graduate School of Medicine, Nippon Medical School, 1-396 Kosugi-cho, Nakahara-ku, Kawasaki, Kanagawa 211-8533, Japan
y-iwai@nms.ac.jp

Received, May 15, 2018
Accepted, August 16, 2018