Enhancement of interleukin-2 production by bovine peripheral blood mononuclear cells treated with the combination of anti-programmed death-ligand 1 and cytotoxic T lymphocyte antigen 4 chimeric monoclonal antibodies

• Published in: Journal of Veterinary Medical Science Vol. 84; no. 1; pp. 6 - 15
• Main Authors: WATARI, Kei, KONNAI, Satoru, OKAGAWA, Tomohiro, MAEKAWA, Naoya, SAJIKI, Yamato, KATO, Yukinari, SUZUKI, Yasuhiko, MURATA, Shiro, OHASHI, Kazuhiko
• Format: Journal Article
• Language: English
• Published: Japan JAPANESE SOCIETY OF VETERINARY SCIENCE 01.01.2022; Japan Science and Technology Agency; The Japanese Society of Veterinary Science
• Subjects: Animals; Antibodies; Antibodies, Monoclonal; Antigens; Apoptosis; B7-H1 Antigen; Cattle; CD80 antigen; CD86 antigen; chimeric antibody; CTLA-4 Antigen; CTLA-4 protein; cytotoxic T lymphocyte antigen 4; Cytotoxicity; Immune response; Immunology; Interleukin 2; Leukocytes, Mononuclear; Ligands; Lymphocytes T; Mice; Monoclonal antibodies; PD-1 protein; PD-L1 protein; Peripheral blood mononuclear cells; Programmed Cell Death 1 Receptor; programmed death-ligand 1; interleukin-2; cattle; programmed death-ligand 1; chimeric antibody; cytotoxic T lymphocyte antigen 4
• ISSN: 0916-7250; 1347-7439; 1347-7439
• DOI: 10.1292/jvms.21-0552

Our previous studies demonstrate the therapeutic efficacy against bovine diseases of an anti-bovine programmed death-ligand 1 (PD-L1) chimeric antibody. In humans, PD-1 and PD-L1 antibodies are more effective when combined with an antibody targeting cytotoxic T lymphocyte antigen 4 (CTLA-4) and these combination therapies are therefore clinically used. Here we generated an anti-bovine CTLA-4 chimeric antibody (chAb) to enhance the therapeutic efficacy of the PD-L1 antibody. We further analyzed the effects of dual blockade of CTLA-4 and PD-1 pathways on T-cell responses. The established anti-bovine CTLA-4 chAb showed comparable blocking activity on the binding of bovine CTLA-4 to CD80 and CD86 as the anti-bovine CTLA-4 mouse monoclonal antibody. Anti-bovine CTLA-4 chAb also significantly increased IL-2 production from bovine peripheral blood mononuclear cells (PBMCs). Further, the combination of anti-CTLA-4 chAb with anti-PD-L1 chAb significantly upregulated IL-2 production by PBMCs. These results suggest that the combination of antibodies have higher potential to enhance immune responses against pathogens compared with single administration.