title: Phase I clinical trial of peptide vaccination with URLC10 and VEGFR1 epitope peptides in patients with advanced gastric cancer.
abstract: Peptide vaccine treatment has attracted attention in recent years as a new therapy option for chemotherapy‑resistant, advanced, unresectable cancer. The safety of peptide vaccination with HLA-A*2402-restricted URLC10-A24-177 and VEGFR1-A12-9 1084 epitope peptides (fixed 2-mg dose) was investigated in a phase I clinical trial of patients with advanced gastric cancer who were refractory to chemotherapy. We determined the HLA genotype of the subjects after enrollment, results of which were held by the evaluation committee and kept from both patients and investigators until completion of the study. The primary end‑point was safety of the peptide vaccination. The secondary end‑points were immunological responses and clinical outcome, which were compared between the HLA-A*2402-positive and HLA-A*2402-negative groups. The peptides were subcutaneously administered on day 1, 8, 15 and 22 within a 28-day treatment cycle. A total of 14 patients was enrolled in this study; 12 of the 14 patients received 4 or more vaccinations (at least 1 course). No patient had a severe treatment-related adverse event. Findings from evaluation of clinical responses after a single course showed that 4 cases had stable disease and 8 cases had progressive disease. The median overall survival time (MST) for the 12 patients was 3.9 months. The MSTs in the HLA-A*2402‑positive and HLA-A*2402‑negative groups were, 4.2 and 3.6 months (p=0.9164), respectively. The results of this study showed that vaccination with URLC10 and VEGFR1 peptides was a safe treatment for advanced gastric cancer. This trial was registered with University Hospital Medical Information Network (UMIN, no. 000002409).
authors.affiliation: Department of Gastroenterology, Juntendo University School of Medicine, Tokyo, Japan.
authors.forename: Yoshie
authors.initials: Y
authors.lastname: Higashihara
authors.affiliation: Department of Gastroenterology, Juntendo University School of Medicine, Tokyo, Japan.
authors.forename: Junko
authors.initials: J
authors.lastname: Kato
authors.affiliation: Department of Gastroenterology, Juntendo University School of Medicine, Tokyo, Japan.
authors.forename: Akihito
authors.initials: A
authors.lastname: Nagahara
authors.affiliation: Department of Gastroenterology, Juntendo University School of Medicine, Tokyo, Japan.
authors.forename: Kentaro
authors.initials: K
authors.lastname: Izumi
authors.affiliation: Department of Gastroenterology, Juntendo University School of Medicine, Tokyo, Japan.
authors.forename: Masae
authors.initials: M
authors.lastname: Konishi
authors.affiliation: Department of Gastroenterology, Juntendo University School of Medicine, Tokyo, Japan.
authors.forename: Tomohiro
authors.initials: T
authors.lastname: Kodani
authors.affiliation: Department of Gastroenterology, Juntendo University School of Medicine, Tokyo, Japan.
authors.forename: Nobuko
authors.initials: N
authors.lastname: Serizawa
authors.affiliation: Department of Gastroenterology, Juntendo University School of Medicine, Tokyo, Japan.
authors.forename: Taro
authors.initials: T
authors.lastname: Osada
authors.affiliation: Department of Gastroenterology, Juntendo University School of Medicine, Tokyo, Japan.
authors.forename: Sumio
authors.initials: S
authors.lastname: Watanabe
mesh_terms: D000328:Adult; D000368:Aged; D019496:Cancer Vaccines / Q000008:administration & dosage*; D000939:Epitopes / Q000008:administration & dosage / Q000276:immunology; D005260:Female; D015234:HLA-A Antigens / Q000276:immunology; D006801:Humans; D008297:Male; D008875:Middle Aged; D013274:Stomach Neoplasms / Q000276:immunology / Q000473:pathology / Q000628:therapy*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D016896:Treatment Outcome; D022223:Vaccines, Subunit / Q000008:administration & dosage*; D040281:Vascular Endothelial Growth Factor Receptor-1 / Q000008:administration & dosage* / Q000235:genetics / Q000276:immunology
chemical_list: D019496:Cancer Vaccines; D000939:Epitopes; D015234:HLA-A Antigens; D022223:Vaccines, Subunit; D040281:Vascular Endothelial Growth Factor Receptor-1