title: Phase I study of a new cancer vaccine of ten mixed peptides for advanced cancer patients.
abstract: A phase I study of a new cancer vaccine (KRM-10), consisting of a mixture of 10 different short peptides, was conducted for patients with advanced gastrointestinal cancers. Primary or secondary endpoints included the dose-limiting toxicity (DLT), or safety and immune responses, respectively. Peptide-specific cytotoxic T lymphocytes (CTL) and immunoglobulin G (IgG), together with soluble inflammatory factors, were measured before and after vaccination. Twenty-one patients were vaccinated with KRM-10 at dose levels of 10 (n = 6), 20 (n = 8) or 30 mg (n = 7) of peptides every week for 6 weeks. No DLT were observed in the dose range evaluated. Common treatment-related adverse events were a grade 1 injection site reaction in 15 patients, and fever in three patients (grade 1 in two patients and grade 2 in one patient). CTL activity to at least one peptide at the time of the third and sixth vaccination increased in 2 and 3 of 6 (10 mg), 2 of 8 and 4 of 6 (20 mg), or 2 and 1 of 6 (30 mg) patients, respectively. IgG levels, at the third and sixth vaccination, were also increased in 1 and 1 of 6 (10 mg), 2 of 8 and 4 of 6 (20 mg), or 1 and 3 of 6 (30 mg) patients, respectively. The KRM-10 vaccine consisting of 20 mg of peptides was determined as the optimal dose for a coming phase II trial because of its safety, and also for demonstrating the most potent activity for augmenting the immune response of the three doses tested. This trial was registered at the UMIN Clinical Trials Registry as UMIN000008820.
authors.affiliation: Gastrointestinal Medical Oncology Division, National Cancer Center Hospital, Tokyo, Japan.
authors.forename: Satoru
authors.initials: S
authors.lastname: Iwasa
authors.affiliation: Gastrointestinal Medical Oncology Division, National Cancer Center Hospital, Tokyo, Japan.
authors.forename: Yasuhide
authors.initials: Y
authors.lastname: Yamada
authors.affiliation: Immunotherapy and Cell Therapy Department, St. Lucas International Hospital, Tokyo, Japan.
authors.forename: Yuji
authors.initials: Y
authors.lastname: Heike
authors.affiliation: Gastrointestinal Medical Oncology Division, National Cancer Center Hospital, Tokyo, Japan.
authors.forename: Hirokazu
authors.initials: H
authors.lastname: Shoji
authors.affiliation: Gastrointestinal Medical Oncology Division, National Cancer Center Hospital, Tokyo, Japan.
authors.forename: Yoshitaka
authors.initials: Y
authors.lastname: Honma
authors.affiliation: Department of Immunology, Kurume University School of Medicine, Kurume, Japan.
authors.forename: Nobukazu
authors.initials: N
authors.lastname: Komatsu
authors.affiliation: Cancer Vaccine Center, Kurume University, Kurume, Japan.
authors.forename: Satoko
authors.initials: S
authors.lastname: Matsueda
authors.affiliation: Research Center for Innovative Cancer Therapy, Kurume University School of Medicine, Kurume, Japan.
authors.forename: Akira
authors.initials: A
authors.lastname: Yamada
authors.affiliation: Department of Surgery, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan.|Division of Pathology, Medical Center of Kurume University, Kurume, Japan.
authors.forename: Michi
authors.initials: M
authors.lastname: Morita
authors.affiliation: Division of Pathology, Medical Center of Kurume University, Kurume, Japan.
authors.forename: Rin
authors.initials: R
authors.lastname: Yamaguchi
authors.affiliation: Department of Surgery, Kurume University School of Medicine, Kurume, Japan.
authors.forename: Natsuki
authors.initials: N
authors.lastname: Tanaka
authors.affiliation: Department of Diagnostic Pathology, Kurume University Hospital, Kurume, Japan.
authors.forename: Akihiko
authors.initials: A
authors.lastname: Kawahara
authors.affiliation: Research Center for Innovative Cancer Therapy, Kurume University School of Medicine, Kurume, Japan.|Department of Diagnostic Pathology, Kurume University Hospital, Kurume, Japan.
authors.forename: Masayoshi
authors.initials: M
authors.lastname: Kage
authors.affiliation: Cancer Vaccine Center, Kurume University, Kurume, Japan.
authors.forename: Shigeki
authors.initials: S
authors.lastname: Shichijo
authors.affiliation: Cancer Vaccine Center, Kanagawa Cancer Center Institute, Yokohama, Japan.
authors.forename: Tetsuro
authors.initials: T
authors.lastname: Sasada
authors.affiliation: Cancer Vaccine Center, Kurume University, Kurume, Japan.
authors.forename: Kyogo
authors.initials: K
authors.lastname: Itoh
mesh_terms: D000368:Aged; D000951:Antigens, Neoplasm / Q000276:immunology; D019496:Cancer Vaccines / Q000008:administration & dosage / Q000009:adverse effects / Q000276:immunology* / Q000627:therapeutic use*; D016207:Cytokines / Q000276:immunology; D005260:Female; D005770:Gastrointestinal Neoplasms / Q000276:immunology* / Q000628:therapy*; D006801:Humans; D007074:Immunoglobulin G / Q000276:immunology; D018836:Inflammation Mediators / Q000276:immunology; D008297:Male; D008875:Middle Aged; D010455:Peptides / Q000276:immunology*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D014611:Vaccination
chemical_list: D000951:Antigens, Neoplasm; D019496:Cancer Vaccines; D016207:Cytokines; D007074:Immunoglobulin G; D018836:Inflammation Mediators; D010455:Peptides
keywords: Cancer vaccine; cytotoxic T-lymphocytes; human leukocyte antigen; peptide; phase I