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
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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
Citation:Mudiyanselage, T. M. R., Fujiwara, D., Michigami, M., Watanabe, S., Ye, Z., Ueda, A., ... & Sugiura, K. (2022). 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. Journal of Veterinary Medical Science, 84(8), 1101-1107.
Date:2022-06-24
Abstract:
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.