Anti-PD-1 antibody and anti-PD-Li antibody -from basic and clinic-

Immune checkpoint inhibitors are most striking among the clinical development of immu- notherapy. These monoclonal antibodies (mAb) restore and augment the anti-tumor immune activities of cytotoxic T cells by mainly blocking immune checkpoint molecules on T cells or their ligands on antigen presenting and tumor cells. Based on preclinical data, many clinical trials have demonstrated the acceptable safety profiles and efficacies in a variety of cancers. Nivolumab and pembrolizumab, humaznized monoclonal antibodies which block pro- grammed death-1 (PD-1) molecule, were approved for advanced melanoma in 2014 and for advanced NSCLC in 2015 and 2016 in Japan. And, nivolumab was also done for advanced re- nal cell cancer and Hodgkin lymphoma in Japan in 2016. And more, phase III trials of anti-PD- 1 mAb and anti-PD-Li mAb for head and neck cancer, ovarian cancer, bladder cancer, gastric cancer, esophageal cancer etc. are ongoing. Several clinical trials have investigated new agents, alone and in combination, for various cancers. In this chapter the history of development of immne checkpoint inhibitors from basic re- search to clinical trial is overviewed.