Identification of peptide vaccine candidates for prostate cancer patients with HLA-A3 supertype alleles.

Abstract

PURPOSE:

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.

EXPERIMENTAL DESIGN:

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.

RESULTS:

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.

CONCLUSIONS:

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.

• Authors: Satoko Matsueda, Hiroko Takedatsu, Akihisa Yao, Masahiro Tanaka, Masanori Noguchi, Kyogo Itoh, Mamoru Harada
• Journal: Clinical cancer research : an official journal of the American Association for Cancer Research (Clin Cancer Res) Vol. 11 Issue 19 Pt 1 Pg. 6933-43 (Oct 01 2005) ISSN: 1078-0432 [Print] United States
• PMID: 16203785 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antigens, Surface
• Cancer Vaccines
• Epitopes, T-Lymphocyte
• HLA-A Antigens
• HLA-A*33 antigen
• HLA-A11 Antigen
• HLA-A3 Antigen
• HLA-A31 antigen
• Immunoglobulin G
• Peptides
• Acid Phosphatase
• prostatic acid phosphatase
• Protein Tyrosine Phosphatases
• FOLH1 protein, human
• Glutamate Carboxypeptidase II
• Prostate-Specific Antigen

Topics

• Acid Phosphatase
• Alleles
• Amino Acid Motifs
• Antigens, Surface (biosynthesis)
• Cancer Vaccines
• Cell Line, Tumor
• Cold Temperature
• Epitopes, T-Lymphocyte (chemistry)
• Glutamate Carboxypeptidase II (biosynthesis)
• HLA-A Antigens (chemistry)
• HLA-A11 Antigen
• HLA-A3 Antigen (biosynthesis, chemistry)
• Humans
• Immunoglobulin G (chemistry)
• Leukocytes, Mononuclear (cytology)
• Male
• Peptides (chemistry)
• Prostate-Specific Antigen (biosynthesis)
• Prostatic Neoplasms (metabolism, pathology)
• Protein Structure, Tertiary
• Protein Tyrosine Phosphatases (biosynthesis)
• T-Lymphocytes, Cytotoxic (cytology)