title: Multiple therapeutic peptide vaccines for patients with advanced gastric cancer.
abstract: We performed a clinical trial using HLA-A24-binding peptide vaccines containing a combination of novel cancer-testis antigens and anti-angiogenic peptides for advanced gastric cancer (GC). Thirty-five GC patients who had shown resistance to the standard therapy were enrolled in this clinical trial using vaccinations with a mixture of multiple peptides derived from DEPDC1, URLC10, FoxM1, Kif20A and VEGFR1. The safety, the overall survival (OS), and the immunological responses based on an ELISPOT assay were determined to assess differences in patients who were HLA-A24-positive [24(+)] and HLA-A24-negative [24(-)]. No severe adverse effects were observed except for severe skin reactions in 4 patients. The differences in OS were not significant between patients who were 24(+) and 24(-). In the 24(+) group, patients who showed T cell responses specific to antigen peptides had a tendency towards better survival than those who showed no response, especially to the DEPDC1 peptide. The patients with local skin reactions had significantly better OS than the others. Peptide vaccine therapy was found to be safe and is expected to induce specific T cell responses in patients with advanced GC. The survival benefit of peptide vaccine monotherapy may not have been shown and further trials are needed to confirm these results.
authors.affiliation: Department of Surgery, Division of Surgical Oncology, Faculty of Medicine, Tottori University, Yonago 683-8504, Japan.
authors.forename: Yoshiyuki
authors.initials: Y
authors.lastname: Fujiwara
authors.affiliation: Department of Surgery, Osaka Medical Center for Cancer and Cardiovascular Diseases, Osaka 537-8511, Japan.
authors.forename: Kaoru
authors.initials: K
authors.lastname: Okada
authors.affiliation: Department of Surgery, Osaka Medical Center for Cancer and Cardiovascular Diseases, Osaka 537-8511, Japan.
authors.forename: Takeshi
authors.initials: T
authors.lastname: Omori
authors.affiliation: Department of Surgery, Osaka Medical Center for Cancer and Cardiovascular Diseases, Osaka 537-8511, Japan.
authors.forename: Keijiro
authors.initials: K
authors.lastname: Sugimura
authors.affiliation: Department of Surgery, Osaka Medical Center for Cancer and Cardiovascular Diseases, Osaka 537-8511, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Miyata
authors.affiliation: Department of Surgery, Osaka Medical Center for Cancer and Cardiovascular Diseases, Osaka 537-8511, Japan.
authors.forename: Masayuki
authors.initials: M
authors.lastname: Ohue
authors.affiliation: Department of Surgery, Osaka Medical Center for Cancer and Cardiovascular Diseases, Osaka 537-8511, Japan.
authors.forename: Shogo
authors.initials: S
authors.lastname: Kobayashi
authors.affiliation: Department of Surgery, Osaka Medical Center for Cancer and Cardiovascular Diseases, Osaka 537-8511, Japan.
authors.forename: Hidenori
authors.initials: H
authors.lastname: Takahashi
authors.affiliation: Department of Pharmacy, Osaka Medical Center for Cancer and Cardiovascular Diseases, Osaka 537-8511, Japan.
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Nakano
authors.affiliation: Department of Pharmacy, Osaka Medical Center for Cancer and Cardiovascular Diseases, Osaka 537-8511, Japan.
authors.forename: Chie
authors.initials: C
authors.lastname: Mochizuki
authors.affiliation: Department of Pharmacy, Osaka Medical Center for Cancer and Cardiovascular Diseases, Osaka 537-8511, Japan.
authors.forename: Katsuji
authors.initials: K
authors.lastname: Shimizu
authors.affiliation: Department of Surgery, Osaka Medical Center for Cancer and Cardiovascular Diseases, Osaka 537-8511, Japan.
authors.forename: Masahiko
authors.initials: M
authors.lastname: Yano
authors.affiliation: Center for Personalized Therapeutics, The University of Chicago, Chicago, IL 60637, USA.
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Nakamura
authors.affiliation: Department of Gastroenterological Surgery, Graduate School of Medicine, Osaka University, Osaka 565-0871, Japan.
authors.forename: Masaki
authors.initials: M
authors.lastname: Mori
authors.affiliation: Department of Gastroenterological Surgery, Graduate School of Medicine, Osaka University, Osaka 565-0871, Japan.
authors.forename: Yuichiro
authors.initials: Y
authors.lastname: Doki
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D020533:Angiogenesis Inhibitors / Q000009:adverse effects / Q000276:immunology / Q000627:therapeutic use; D019496:Cancer Vaccines / Q000008:administration & dosage* / Q000276:immunology; D018572:Disease-Free Survival; D005260:Female; D000072278:Forkhead Box Protein M1 / Q000276:immunology / Q000627:therapeutic use; D020690:GTPase-Activating Proteins / Q000276:immunology / Q000627:therapeutic use; D059871:HLA-A24 Antigen / Q000276:immunology* / Q000627:therapeutic use; D006801:Humans; D053208:Kaplan-Meier Estimate; D016547:Kinesins / Q000276:immunology / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000276:immunology / Q000627:therapeutic use; D009367:Neoplasm Staging; D013274:Stomach Neoplasms / Q000276:immunology / Q000473:pathology / Q000628:therapy*; D016896:Treatment Outcome; D022223:Vaccines, Subunit / Q000008:administration & dosage* / Q000009:adverse effects / Q000276:immunology; D040281:Vascular Endothelial Growth Factor Receptor-1 / Q000276:immunology / Q000627:therapeutic use
chemical_list: D020533:Angiogenesis Inhibitors; D019496:Cancer Vaccines; C584411:DEPDC1 protein, human; C107585:FOXM1 protein, human; D000072278:Forkhead Box Protein M1; D020690:GTPase-Activating Proteins; D059871:HLA-A24 Antigen; C410089:KIF20A protein, human; D009363:Neoplasm Proteins; D022223:Vaccines, Subunit; D040281:Vascular Endothelial Growth Factor Receptor-1; D016547:Kinesins