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Published on: July 7, 2023
New peptide vaccine candidates for epithelial cancer patients with HLA-A3 supertype alleles
Satoko Matsueda1, Hiroko Takedatsu, Tetsuro Sasada
1*Department of Immunology, Karume University School of Medicine, Karume, Fukuoka, Japan.
Abstract:
We previously identified 2 cancer-associated antigens, immediate early response gene X-1 (IEX) and small GTPase (Ran), and their 5 epitopes using human leukocyte antigen (HLA)-A33-restricted and tumor-infiltrating T cells from a colon cancer patient. In this study, we examined whether or not these peptides can induce cytotoxic T lymphocytes (CTLs) in HLA-A11+ or HLA-A31+ epithelial cancer patients because the HLA-A11, HLA-A31, and HLA-A33 alleles share binding motifs as an HLA-A3 supertype family, which is widely distributed in many ethnic populations. Among them, the 2 peptides, IEX 47-56 and IEX 61-69, induced peptide-specific CTLs from peripheral blood mononuclear cells of cancer patients with the HLA-A11 and HLA-A31 alleles more efficiently than the other 3 peptides. Antibody blocking and cold inhibition experiments revealed that the cytotoxicity of peptide-induced CTLs against cancer cells was attributable to peptide-specific and CD8+ T cells. Together with our previous findings, these results indicate that the 2 IEX peptides could be appropriate vaccine candidates for HLA-A11, HLA-A31, and HLA-A33 positive epithelial cancer patients. This information could expand the chance of a peptide-based cancer vaccine for epithelial cancer patients of many ethnic populations.
Insights
Two specific peptides from the immediate early response gene X-1 (IEX) effectively induced cancer-fighting T cells in patients with common HLA-A11, HLA-A31, and HLA-A33 alleles, suggesting potential as cancer vaccine candidates.
Area of Science:
- Immunology
- Oncology
- Vaccinology
Background:
- Previous identification of two cancer-associated antigens, immediate early response gene X-1 (IEX) and small GTPase (Ran), and five epitopes.
- Focus on HLA-A3 supertype alleles (HLA-A11, HLA-A31, HLA-A33) due to shared binding motifs and wide ethnic distribution.
Purpose of the Study:
- To investigate the potential of previously identified IEX and Ran peptides to induce cytotoxic T lymphocytes (CTLs) in epithelial cancer patients with HLA-A11 or HLA-A31 alleles.
- To evaluate the efficacy of specific IEX peptides as vaccine candidates for a broader population of epithelial cancer patients.
Main Methods:
- Testing peptide-induced CTL induction in peripheral blood mononuclear cells (PBMCs) from HLA-A11+ and HLA-A31+ epithelial cancer patients.
- Utilizing antibody blocking and cold inhibition assays to confirm the mechanism of cytotoxicity mediated by CD8+ T cells.
Main Results:
- Two IEX peptides (IEX 47-56 and IEX 61-69) demonstrated efficient induction of peptide-specific CTLs in PBMCs from HLA-A11 and HLA-A31 positive cancer patients.
- Cytotoxicity was confirmed to be mediated by peptide-specific, CD8+ T cells against cancer cells.
Conclusions:
- The two IEX peptides are promising vaccine candidates for epithelial cancer patients positive for HLA-A11, HLA-A31, and HLA-A33 alleles.
- These findings broaden the applicability of peptide-based cancer vaccines across diverse ethnic populations.
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