Journal of Nippon Medical School
Online ISSN : 1347-3409
Print ISSN : 1345-4676
ISSN-L : 1345-4676
Development of Cancer Immunotherapy Targeting the PD-1 Pathway
Naomi KamimuraAlexander M. WolfYoshiko Iwai
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2019 Volume 86 Issue 1 Pages 10-14


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.

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© 2019 by the Medical Association of Nippon Medical School
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