PMID- 18043580 OWN - NLM STAT- MEDLINE DCOM- 20080214 LR - 20211020 IS - 0007-0920 (Print) IS - 1532-1827 (Electronic) IS - 0007-0920 (Linking) VI - 97 IP - 12 DP - 2007 Dec 17 TI - Identification of Lck-derived peptides applicable to anti-cancer vaccine for patients with human leukocyte antigen-A3 supertype alleles. PG - 1648-54 AB - The identification of peptide vaccine candidates to date has been focused on human leukocyte antigen (HLA)-A2 and -A24 alleles. In this study, we attempted to identify cytotoxic T lymphocyte (CTL)-directed Lck-derived peptides applicable to HLA-A11(+), -A31(+), or -A33(+) cancer patients, because these HLA-A alleles share binding motifs, designated HLA-A3 supertype alleles, and because the Lck is preferentially expressed in metastatic cancer. Twenty-one Lck-derived peptides were prepared based on the binding motif to the HLA-A3 supertype alleles. They were first screened for their recognisability by immunoglobulin G (IgG) in the plasma of prostate cancer patients, and the selected candidates were subsequently tested for their potential to induce peptide-specific CTLs from peripheral blood mononuclear cells of HLA-A3 supertype(+) cancer patients. As a result, four Lck peptides were frequently recognised by IgGs, and three of them - Lck(90-99), Lck(449-458), and Lck(450-458) - efficiently induced peptide-specific and cancer-reactive CTLs. Their cytotoxicity towards cancer cells was mainly ascribed to HLA class I-restricted and peptide-specific CD8(+) T cells. These results indicate that these three Lck peptides are applicable to HLA-A3 supertype(+) cancer patients, especially those with metastasis. This information could facilitate the development of peptide-based anti-cancer vaccine for patients with alleles other than HLA-A2 and -A24. FAU - Naito, M AU - Naito M AD - Department of Immunology, Kurume University School of Medicine, 67 Asahi-machi, Kurume, Fukuoka 830-0011, Japan. haramano@med.shimane-u.ac.jp FAU - Komohara, Y AU - Komohara Y FAU - Ishihara, Y AU - Ishihara Y FAU - Noguchi, M AU - Noguchi M FAU - Yamashita, Y AU - Yamashita Y FAU - Shirakusa, T AU - Shirakusa T FAU - Yamada, A AU - Yamada A FAU - Itoh, K AU - Itoh K FAU - Harada, M AU - Harada M LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20071127 PL - England TA - Br J Cancer JT - British journal of cancer JID - 0370635 RN - 0 (Cancer Vaccines) RN - 0 (HLA-A3 Antigen) RN - 0 (Immunoglobulin G) RN - 0 (Peptides) RN - EC 2.7.10.2 (Lymphocyte Specific Protein Tyrosine Kinase p56(lck)) SB - IM MH - Cancer Vaccines/*therapeutic use MH - Cell Line, Tumor MH - HLA-A3 Antigen/*genetics MH - Humans MH - Immunoglobulin G/analysis MH - Lymphocyte Specific Protein Tyrosine Kinase p56(lck)/*immunology MH - Male MH - Neoplasms/genetics/immunology/*therapy MH - *Peptides MH - Prostatic Neoplasms/genetics/immunology MH - T-Lymphocytes, Cytotoxic/*immunology PMC - PMC2360277 EDAT- 2007/11/29 09:00 MHDA- 2008/02/15 09:00 PMCR- 2008/12/17 CRDT- 2007/11/29 09:00 PHST- 2007/11/29 09:00 [pubmed] PHST- 2008/02/15 09:00 [medline] PHST- 2007/11/29 09:00 [entrez] PHST- 2008/12/17 00:00 [pmc-release] AID - 6604071 [pii] AID - 10.1038/sj.bjc.6604071 [doi] PST - ppublish SO - Br J Cancer. 2007 Dec 17;97(12):1648-54. doi: 10.1038/sj.bjc.6604071. Epub 2007 Nov 27.