title: Immunological effects of the anti-programmed death-1 antibody on human peripheral blood mononuclear cells.
abstract: Immune checkpoint antibody-mediated blockade has gained attention as a new cancer immunotherapy strategy. Accumulating evidence suggests that this therapy imparts a survival benefit to metastatic melanoma and non-small cell lung cancer patients. A substantial amount of data on immune checkpoint antibodies has been collected from clinical trials; however, the direct effect of the antibodies on human peripheral blood mononuclear cells (PBMCs) has not been exclusively investigated. In this study, we developed an anti-programmed death-1 (PD-1) antibody (with biosimilarity to nivolumab) and examined the effects of the antibody on PBMCs derived from cancer patients. Specifically, we investigated the effects of the anti-PD-1 antibody on proliferation, cytokine production, cytotoxic T lymphocytes (CTL) and regulatory T cells. These investigations yielded several important results. First, the anti-PD-1 antibody had no obvious effect on resting PBMCs; however, high levels of the anti-PD-1 antibody partly stimulated PBMC proliferation when accompanied by an anti-CD3 antibody. Second, the anti-PD-1 antibody restored the growth inhibition of anti-CD3 Ab-stimulated PBMCs mediated by PD-L1. Third, the anti-PD-1 antibody exhibited a moderate inhibitory effect on the induction of myeloid-derived suppressor cells (MDSCs) by anti-CD3 antibody stimulation. Additionally, the presence of the anti-PD-1 antibody promoted antigen-specific CTL induction, which suggests that combining anti-PD-1 antibody and conventional immunotherapy treatments may have beneficial effects. These results indicate that specific cellular immunological mechanisms are partly responsible for the antitumor effect exhibited by the anti-PD-1 antibody against advanced cancers in clinical trials.
authors: Immunotherapy Division, Shizuoka Cancer Center Research Institute, Nagaizumi-cho, Sunto-gun, Shizuoka 411-8777, Japan.
authors: Yasuto
authors: Y
authors: Akiyama
authors: Immunotherapy Division, Shizuoka Cancer Center Research Institute, Nagaizumi-cho, Sunto-gun, Shizuoka 411-8777, Japan.
authors: Chizu
authors: C
authors: Nonomura
authors: Immunotherapy Division, Shizuoka Cancer Center Research Institute, Nagaizumi-cho, Sunto-gun, Shizuoka 411-8777, Japan.
authors: Ryota
authors: R
authors: Kondou
authors: Immunotherapy Division, Shizuoka Cancer Center Research Institute, Nagaizumi-cho, Sunto-gun, Shizuoka 411-8777, Japan.
authors: Haruo
authors: H
authors: Miyata
authors: Immunotherapy Division, Shizuoka Cancer Center Research Institute, Nagaizumi-cho, Sunto-gun, Shizuoka 411-8777, Japan.
authors: Tadashi
authors: T
authors: Ashizawa
authors: Immunotherapy Division, Shizuoka Cancer Center Research Institute, Nagaizumi-cho, Sunto-gun, Shizuoka 411-8777, Japan.
authors: Chie
authors: C
authors: Maeda
authors: Division of Neurosurgery, Shizuoka Cancer Center Hospital, Nagaizumi-cho, Sunto-gun, Shizuoka 411-8777, Japan.
authors: Koichi
authors: K
authors: Mitsuya
authors: Division of Neurosurgery, Shizuoka Cancer Center Hospital, Nagaizumi-cho, Sunto-gun, Shizuoka 411-8777, Japan.
authors: Nakamasa
authors: N
authors: Hayashi
authors: Division of Neurosurgery, Shizuoka Cancer Center Hospital, Nagaizumi-cho, Sunto-gun, Shizuoka 411-8777, Japan.
authors: Yoko
authors: Y
authors: Nakasu
authors: Office of The President, Shizuoka Cancer Center Hospital, Nagaizumi-cho, Sunto-gun, Shizuoka 411-8777, Japan.
authors: Ken
authors: K
authors: Yamaguchi
mesh_terms: D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal / Q000378:metabolism / Q000494:pharmacology*; D049109:Cell Proliferation / Q000187:drug effects; D016207:Cytokines / Q000378:metabolism*; D005260:Female; D005910:Glioma / Q000276:immunology*; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000187:drug effects*; D008297:Male; D008875:Middle Aged; D061026:Programmed Cell Death 1 Receptor / Q000276:immunology*; D013602:T-Lymphocytes, Cytotoxic / Q000187:drug effects / Q000276:immunology; D050378:T-Lymphocytes, Regulatory / Q000187:drug effects / Q000276:immunology; D014407:Tumor Cells, Cultured
chemical_list: D000911:Antibodies, Monoclonal; D016207:Cytokines; C105992:PDCD1 protein, human; D061026:Programmed Cell Death 1 Receptor