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Generation of molecular-targeting helix-loop-helix peptides for inhibition of the interaction between cytotoxic T-lymphocyte-associated protein 4 and B7 in the dog

Blocking the interaction between CD28 and B7 by cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) is a potent immune checkpoint that prevents damage to host tissues from excessive immune responses. However, it also significantly diminishes immune responses against cancers and allows cancer cell g...

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Autores principales: RAMANAYAKE MUDIYANSELAGE, Tharanga MR, FUJIWARA, Daisuke, MICHIGAMI, Masataka, WATANABE, Shunichi, YE, Zhengmao, UEDA, Atsuko, KANEGI, Ryoji, HATOYA, Shingo, FUJII, Ikuo, SUGIURA, Kikuya
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The Japanese Society of Veterinary Science 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9412056/
https://www.ncbi.nlm.nih.gov/pubmed/35753760
http://dx.doi.org/10.1292/jvms.21-0318
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author RAMANAYAKE MUDIYANSELAGE, Tharanga MR
FUJIWARA, Daisuke
MICHIGAMI, Masataka
WATANABE, Shunichi
YE, Zhengmao
UEDA, Atsuko
KANEGI, Ryoji
HATOYA, Shingo
FUJII, Ikuo
SUGIURA, Kikuya
author_facet RAMANAYAKE MUDIYANSELAGE, Tharanga MR
FUJIWARA, Daisuke
MICHIGAMI, Masataka
WATANABE, Shunichi
YE, Zhengmao
UEDA, Atsuko
KANEGI, Ryoji
HATOYA, Shingo
FUJII, Ikuo
SUGIURA, Kikuya
author_sort RAMANAYAKE MUDIYANSELAGE, Tharanga MR
collection PubMed
description Blocking the interaction between CD28 and B7 by cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) is a potent immune checkpoint that prevents damage to host tissues from excessive immune responses. However, it also significantly diminishes immune responses against cancers and allows cancer cell growth. This study found that recombinant (r) human (h) CTLA-4 specifically binds to canine dendritic cells (DCs) and suppresses the responses of canine T cells to allogeneic DCs. ERY2-4, a peptide targeting rhCTLA-4 selected from a yeast-displayed library of helix-loop-helix (HLH) peptides and improved to have a binding affinity to rhCTLA-4 as strong as that of rhB7, inhibited the binding of rhCTLA-4 to canine DCs. Furthermore, the targeting peptide significantly enhanced the response of canine T cells to allogeneic DCs. These results suggest that the CTLA-4-targeting peptide enhances canine T cell activity by blocking the interaction between canine CTLA-4 on T cells and canine B7 on DCs. This study demonstrates the generation of a new type of immune checkpoint inhibitor, which may be applicable to cancer therapy in dogs.
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spelling pubmed-94120562022-08-30 Generation of molecular-targeting helix-loop-helix peptides for inhibition of the interaction between cytotoxic T-lymphocyte-associated protein 4 and B7 in the dog RAMANAYAKE MUDIYANSELAGE, Tharanga MR FUJIWARA, Daisuke MICHIGAMI, Masataka WATANABE, Shunichi YE, Zhengmao UEDA, Atsuko KANEGI, Ryoji HATOYA, Shingo FUJII, Ikuo SUGIURA, Kikuya J Vet Med Sci Immunology Blocking the interaction between CD28 and B7 by cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) is a potent immune checkpoint that prevents damage to host tissues from excessive immune responses. However, it also significantly diminishes immune responses against cancers and allows cancer cell growth. This study found that recombinant (r) human (h) CTLA-4 specifically binds to canine dendritic cells (DCs) and suppresses the responses of canine T cells to allogeneic DCs. ERY2-4, a peptide targeting rhCTLA-4 selected from a yeast-displayed library of helix-loop-helix (HLH) peptides and improved to have a binding affinity to rhCTLA-4 as strong as that of rhB7, inhibited the binding of rhCTLA-4 to canine DCs. Furthermore, the targeting peptide significantly enhanced the response of canine T cells to allogeneic DCs. These results suggest that the CTLA-4-targeting peptide enhances canine T cell activity by blocking the interaction between canine CTLA-4 on T cells and canine B7 on DCs. This study demonstrates the generation of a new type of immune checkpoint inhibitor, which may be applicable to cancer therapy in dogs. The Japanese Society of Veterinary Science 2022-06-24 2022-08 /pmc/articles/PMC9412056/ /pubmed/35753760 http://dx.doi.org/10.1292/jvms.21-0318 Text en ©2022 The Japanese Society of Veterinary Science https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution Non-Commercial No Derivatives (by-nc-nd) License. (CC-BY-NC-ND 4.0: https://creativecommons.org/licenses/by-nc-nd/4.0/)
spellingShingle Immunology
RAMANAYAKE MUDIYANSELAGE, Tharanga MR
FUJIWARA, Daisuke
MICHIGAMI, Masataka
WATANABE, Shunichi
YE, Zhengmao
UEDA, Atsuko
KANEGI, Ryoji
HATOYA, Shingo
FUJII, Ikuo
SUGIURA, Kikuya
Generation of molecular-targeting helix-loop-helix peptides for inhibition of the interaction between cytotoxic T-lymphocyte-associated protein 4 and B7 in the dog
title Generation of molecular-targeting helix-loop-helix peptides for inhibition of the interaction between cytotoxic T-lymphocyte-associated protein 4 and B7 in the dog
title_full Generation of molecular-targeting helix-loop-helix peptides for inhibition of the interaction between cytotoxic T-lymphocyte-associated protein 4 and B7 in the dog
title_fullStr Generation of molecular-targeting helix-loop-helix peptides for inhibition of the interaction between cytotoxic T-lymphocyte-associated protein 4 and B7 in the dog
title_full_unstemmed Generation of molecular-targeting helix-loop-helix peptides for inhibition of the interaction between cytotoxic T-lymphocyte-associated protein 4 and B7 in the dog
title_short Generation of molecular-targeting helix-loop-helix peptides for inhibition of the interaction between cytotoxic T-lymphocyte-associated protein 4 and B7 in the dog
title_sort generation of molecular-targeting helix-loop-helix peptides for inhibition of the interaction between cytotoxic t-lymphocyte-associated protein 4 and b7 in the dog
topic Immunology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9412056/
https://www.ncbi.nlm.nih.gov/pubmed/35753760
http://dx.doi.org/10.1292/jvms.21-0318
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