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


METHODS
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.
Matsueda
Satoko
S
Department of Immunology, Kurume University School of Medicine, Kurume, Fukuoka, Japan.
Takedatsu
Hiroko
H
Yao
Akihisa
A
Tanaka
Masahiro
M
Noguchi
Masanori
M
Itoh
Kyogo
K
Harada
Mamoru
M
D000135:Acid Phosphatase; D000483:Alleles; D020816:Amino Acid Motifs; D000954:Antigens, Surface / Q000096:biosynthesis; D019496:Cancer Vaccines; D045744:Cell Line, Tumor; D003080:Cold Temperature; D018984:Epitopes, T-Lymphocyte / Q000737:chemistry; D043425:Glutamate Carboxypeptidase II / Q000096:biosynthesis; D015234:HLA-A Antigens / Q000737:chemistry; D059870:HLA-A11 Antigen; D015791:HLA-A3 Antigen / Q000096:biosynthesis / Q000737:chemistry*; D006801:Humans; D007074:Immunoglobulin G / Q000737:chemistry; D007963:Leukocytes, Mononuclear / Q000166:cytology; D008297:Male; D010455:Peptides / Q000737:chemistry*; D017430:Prostate-Specific Antigen / Q000096:biosynthesis; D011471:Prostatic Neoplasms / Q000378:metabolism* / Q000473:pathology; D017434:Protein Structure, Tertiary; D017027:Protein Tyrosine Phosphatases / Q000096:biosynthesis; D013602:T-Lymphocytes, Cytotoxic / Q000166:cytology
D000954:Antigens, Surface; D019496:Cancer Vaccines; D018984:Epitopes, T-Lymphocyte; D015234:HLA-A Antigens; C082945:HLA-A*33 antigen; D059870:HLA-A11 Antigen; D015791:HLA-A3 Antigen; C069527:HLA-A31 antigen; D007074:Immunoglobulin G; D010455:Peptides; D000135:Acid Phosphatase; C428439:prostatic acid phosphatase; D017027:Protein Tyrosine Phosphatases; C473848:FOLH1 protein, human; D043425:Glutamate Carboxypeptidase II; D017430:Prostate-Specific Antigen