Immunological effects of the anti-programmed death-1 antibody on human peripheral blood mononuclear cells

• Published in: International journal of oncology Vol. 49; no. 3; pp. 1099 - 1107
• Main Authors: Akiyama, Yasuto, Nonomura, Chizu, Kondou, Ryota, Miyata, Haruo, Ashizawa, Tadashi, Maeda, Chie, Mitsuya, Koichi, Hayashi, Nakamasa, Nakasu, Yoko, Yamaguchi, Ken
• Format: Journal Article
• Language: English
• Published: Greece D.A. Spandidos 01.09.2016; Spandidos Publications; Spandidos Publications UK Ltd
• Subjects: Adult; Aged; anti-PD-1 antibody; Antibodies, Monoclonal - metabolism; Antibodies, Monoclonal - pharmacology; Antigens; Cancer therapies; Carcinogenesis; Cell growth; Cell Proliferation - drug effects; checkpoint antibody; Clinical trials; Cloning; Cytokines - metabolism; Female; Genetic aspects; Glioma - immunology; human peripheral blood mononuclear cell; Humans; Immune response; Immune system; Immunoglobulins; Immunology; Immunotherapy; Leukocytes, Mononuclear - drug effects; Ligands; Lymphocytes; Male; Melanoma; Metastasis; Middle Aged; Monoclonal antibodies; myeloid-derived suppressor cell; Patients; Programmed Cell Death 1 Receptor - immunology; Proteins; regulatory T cells; Studies; T-Lymphocytes, Cytotoxic - drug effects; T-Lymphocytes, Cytotoxic - immunology; T-Lymphocytes, Regulatory - drug effects; T-Lymphocytes, Regulatory - immunology; Targeted cancer therapy; Tumor Cells, Cultured; Tumors
• ISSN: 1019-6439; 1791-2423
• DOI: 10.3892/ijo.2016.3586

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.