Abstract
The peptide vaccine candidates identified to date have been focused on the HLA-A2 and HLA-A24 alleles. The HLA-A11, HLA-A31, and HLA-A33 alleles share binding motifs and belong to an HLA-A3 supertype family. In this study, we attempted to identify CTL-directed peptide candidates, derived from prostate-related antigens and shared by HLA-A11+, HLA-A31+, and HLA-A33+ prostate cancer patients. Based on the binding motif to the HLA-A3 supertype alleles, 42 peptides were prepared from prostate-specific antigen (PSA), prostate-specific membrane antigen (PSMA), and prostatic acid phosphatase (PAP). These peptides were first screened for their ability to be recognized by immunoglobulin G (IgG) of prostate cancer patients and subsequently for the potential to induce peptide-specific and prostate cancer-reactive CTLs from peripheral blood mononuclear cells (PBMC) of cancer patients with the HLA-A11, HLA-A31, and HLA-A33 alleles. Five peptide candidates, including the PSA(16-24), PAP(155-163), PAP(248-257), PSMA(207-215), and PSMA(431-440) peptides, were frequently recognized by IgGs of prostate cancer patients. These peptides efficiently induced peptide-specific and prostate cancer-reactive CTLs from PBMCs of cancer patients with the HLA-A11, HLA-A31, and HLA-A33 alleles. Antibody blocking and cold inhibition experiments revealed that the HLA-A3 supertype-restricted cytotoxicity against prostate cancer cells could be ascribed to peptide-specific and CD8+ T cells. We identified prostate-related antigen-derived new peptide candidates for HLA-A11-, HLA-A31-, and HLA-A33-positive prostate cancer patients. This information could facilitate the development of a peptide-based anticancer vaccine for patients with alleles other than HLA-A2 and HLA-A24.
Highlights
The peptide vaccine candidates identified to date have been focused on the HLA-A2 and HLA-A24 alleles.The HLA-A11, HLA-A31, and HLA-A33 alleles share binding motifs and belong to an HLA-A3 supertype family
We prepared 42 peptides derived from prostate-specific antigen (PSA), prostatic acid phosphatase (PAP), and prostate-specific membrane antigen (PSMA), based on the binding motifs to the HLA-A3, HLA-A11, HLA-A31, HLA-A33, and HLA-A68.1 molecules (Table 1)
We examined the ability of these peptides to be recognized by immunoglobulin G (IgG) of prostate cancer patients, because we have previously observed that IgGs reactive to CTL-directed peptides are frequently detected in the plasma of patients with several types of cancers [22, 23], and that IgGs reactive to PSA-derived or PSMA-derived CTL-directed peptides are detectable in the plasma of prostate cancer patients and healthy donors [24, 25]
Summary
The peptide vaccine candidates identified to date have been focused on the HLA-A2 and HLA-A24 alleles.The HLA-A11, HLA-A31, and HLA-A33 alleles share binding motifs and belong to an HLA-A3 supertype family. We attempted to identify CTL-directed peptide candidates, derived from prostate-related antigens and shared by HLA-A11+, HLA-A31+, and HLA-A33+ prostate cancer patients. Results: Five peptide candidates, including the PSA16-24, PAP155-163, PAP248-257, PSMA207-215, and PSMA431-440 peptides, were frequently recognized by IgGs of prostate cancer patients These peptides efficiently induced peptide-specific and prostate cancer ^ reactive CTLs from PBMCs of cancer patients with the HLA-A11, HLA-A31, and HLA-A33 alleles. Conclusions: We identified prostate-related antigen-derived new peptide candidates for HLAA11-, HLA-A31-, and HLA-A33-positive prostate cancer patients.This information could facilitate the development of a peptide-based anticancer vaccine for patients with alleles other than HLAA2 and HLA-A24. We tried to identify prostate-related antigen-derived peptides that are applicable for HLA-A3 supertype+ prostate cancer patients, to facilitate the development of a peptide-based anticancer vaccine for prostate cancer patients with alleles other than HLA-A2 and HLA-A24
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
