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

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 thes...

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Published inJournal 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
LanguageEnglish
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
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Abstract 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.
AbstractList 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.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.
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.
ArticleNumber 21-0552
Author OHASHI, Kazuhiko
KATO, Yukinari
MURATA, Shiro
WATARI, Kei
KONNAI, Satoru
MAEKAWA, Naoya
SUZUKI, Yasuhiko
OKAGAWA, Tomohiro
SAJIKI, Yamato
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  organization: Department of Disease Control, Faculty of Veterinary Medicine, Hokkaido University, Sapporo, Hokkaido 060-0818, Japan
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  fullname: OKAGAWA, Tomohiro
  organization: Department of Advanced Pharmaceutics, Faculty of Veterinary Medicine, Hokkaido University, Sapporo, Hokkaido 060-0818, Japan
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  fullname: MAEKAWA, Naoya
  organization: Department of Advanced Pharmaceutics, Faculty of Veterinary Medicine, Hokkaido University, Sapporo, Hokkaido 060-0818, Japan
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  fullname: SAJIKI, Yamato
  organization: Department of Disease Control, Faculty of Veterinary Medicine, Hokkaido University, Sapporo, Hokkaido 060-0818, Japan
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  organization: Department of Antibody Drug Development, Tohoku University Graduate School of Medicine, Sendai, Miyagi 980-8575, Japan
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  organization: Department of Advanced Pharmaceutics, Faculty of Veterinary Medicine, Hokkaido University, Sapporo, Hokkaido 060-0818, Japan
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  organization: Department of Disease Control, Faculty of Veterinary Medicine, Hokkaido University, Sapporo, Hokkaido 060-0818, Japan
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Issue 1
Keywords interleukin-2
cattle
programmed death-ligand 1
chimeric antibody
cytotoxic T lymphocyte antigen 4
Language English
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18. Nishimori, A., Konnai, S., Okagawa, T., Maekawa, N., Ikebuchi, R., Goto, S., Sajiki, Y., Suzuki, Y., Kohara, J., Ogasawara, S.,
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Snippet Our previous studies demonstrate the therapeutic efficacy against bovine diseases of an anti-bovine programmed death-ligand 1 (PD-L1) chimeric antibody. In...
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pubmed
crossref
jstage
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SubjectTerms 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
Title 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
URI https://www.jstage.jst.go.jp/article/jvms/84/1/84_21-0552/_article/-char/en
https://www.ncbi.nlm.nih.gov/pubmed/34789592
https://www.proquest.com/docview/2624693171
https://www.proquest.com/docview/2599074866
https://pubmed.ncbi.nlm.nih.gov/PMC8810316
Volume 84
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