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The HLA-A11 or -A33 allele is found in approximately 18% or 10% of the Asian population, respectively, but each of which is a minor allele worldwide, and therefore no clinical trials were previously conducted. To develop a therapeutic peptide vaccine for each of them, we investigated immunological responses of advanced cancer patients with the HLA-A11+/A11+ ( n = 18) or -A33+/A33+ ( n = 13) allele to personalized peptide vaccine ( PPV) regimens. The primary sites of HLA-A11+/A11+ or -A33+/A33+ patients were the colon ( n = 4 or 2), stomach (2 or 3), breast (3 or 2), lung and pancreas (2 or 2), and so on. For PPV, a maximum of four peptides were selected from nine different peptides capable of binding to HLA-A11 and -A33 molecules based on the pre-existing peptide-specific IgG responses. There were no severe adverse events related to PPV. At the end of the first cycle, peptide-specific CTL responses were augmented in 4/12 or 2/9 of HLA-A11+/A11+ or -A33+/A33+ patients, while peptide-specific IgG responses were augmented in 6/14 or 4/10 patients, respectively. Clinical responses consisted of four stable diseases and 14 progressive diseases in HLA-A11+/A11+patients, versus seven and six in -A33+/A33+patients, respectively. Further clinical study of PPV could be recommended because of the safety and positive immunological responses. [ABSTRACT FROM AUTHOR]

The present study attempted to identify T helper epitope long peptides capable of inducing cytotoxic T lymphocytes (CTL) from Lck antigen (p56Lck), the src family tyrosine kinase, which is known to be aberrantly expressed in metastatic cancers cells, in order to develop a long peptide-based cancer vaccine for HLA-A2+ cancer patients. Based on the biding motif to the HLA-DR and HLA-A2 alleles, 94 peptides were prepared from the Lck antigen. These peptides were screened for their reactivity to immunoglobulin G (IgG) from plasma of cancer patients, followed by testing of their ability to induce both CD4+ and CD8+ T lymphocytes showing not only peptide-specific IFN-γ production but cytotoxicity against HLA-A2+ cancer cells from peripheral blood mononuclear cells (PBMC) of HLA-A2+ cancer patients. Among 94 peptides tested, the three T helper epitope long peptides and their inner CTL epitope short peptides with HLA-A2 binding motifs were frequently recognized by IgG of cancer patients, and efficiently induced both CD4+ IFN-γ+ and CD8+ IFN-γ+ T lymphocytes. Patients' PBMC stimulated with these long peptides showed cytotoxicity against HLA-A2+ Lck+ cancer cells in HLA-class I and HLA-class II dependent manners. These three peptides might be useful for long peptide-based vaccines for HLA-A2+cancer patients with Lck+ tumor cells. [ABSTRACT FROM AUTHOR]

The HLA-A11 or -A33 allele is found in approximately 18% or 10% of the Asian population, respectively, but each of which is a minor allele worldwide, and therefore no clinical trials were previously conducted. To develop a therapeutic peptide vaccine for each of them, we investigated immunological responses of advanced cancer patients with the HLA-A11 + /A11 + (n = 18) or -A33 + /A33 + (n = 13) allele to personalized peptide vaccine (PPV) regimens. The primary sites of HLA-A11+/A11+ or -A33+/A33+ patients were the colon (n = 4 or 2), stomach (2 or 3), breast (3 or 2), lung and pancreas (2 or 2), and so on. For PPV, a maximum of four peptides were selected from nine different peptides capable of binding to HLA-A11 and -A33 molecules based on the pre-existing peptide-specific IgG responses. There were no severe adverse events related to PPV. At the end of the first cycle, peptide-specific CTL responses were augmented in 4/12 or 2/9 of HLA-A11 + /A11 + or -A33 + /A33 + patients, while peptide-specific IgG responses were augmented in 6/14 or 4/10 patients, respectively. Clinical responses consisted of four stable diseases and 14 progressive diseases in HLA-A11 + /A11 + patients, versus seven and six in -A33 + /A33 + patients, respectively. Further clinical study of PPV could be recommended because of the safety and positive immunological responses., (© 2017 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.)