title: Phase I clinical trial of a five-peptide cancer vaccine combined with cyclophosphamide in advanced solid tumors.
abstract: We designed a phase I trial to investigate the safety, immune responses and clinical benefits of a five-peptide cancer vaccine in combination with chemotherapy. Study subjects were patients positive for HLA-A2402 with locally advanced, metastatic, and/or recurrent gastrointestinal, lung or cervical cancer. Eighteen patients including nine cases of colorectal cancer were treated with escalating doses of cyclophosphamide 4days before vaccination. Five HLA-A2402-restricted, tumor-associated antigen (TAA) epitope peptides from KOC1, TTK, URLC10, DEPDC1 and MPHOSPH1 were injected weekly for 4weeks. Treatment was well tolerated without any adverse events above grade 3. Analysis of peripheral blood lymphocytes showed that the number of regulatory T cells dropped from baseline after administration of cyclophosphamide and confirmed that TAA-specific T cell responses were associated significantly with longer overall survival. This phase I clinical trial demonstrated safety and promising immune responses that correlated with vaccine-induced T-cell responses. Therefore, this approach warrants further clinical studies.
authors.affiliation: Department of Advanced Cell and Molecular Therapy, Kyushu University Hospital, Fukuoka, Japan.
authors.forename: Mutsunori
authors.initials: M
authors.lastname: Murahashi
authors.affiliation: Department of Advanced Cell and Molecular Therapy, Kyushu University Hospital, Fukuoka, Japan.
authors.forename: Yasuki
authors.initials: Y
authors.lastname: Hijikata
authors.affiliation: Department of Advanced Cell and Molecular Therapy, Kyushu University Hospital, Fukuoka, Japan.
authors.forename: Kazunari
authors.initials: K
authors.lastname: Yamada
authors.affiliation: Division of Molecular and Clinical Genetics, Medical Institute of Bioregulation, Kyushu University, Fukuoka, Japan.
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Tanaka
authors.affiliation: Digital Medicine Initiative, Kyushu University, Fukuoka, Japan.
authors.forename: Junji
authors.initials: J
authors.lastname: Kishimoto
authors.affiliation: Division of Molecular and Clinical Genetics, Medical Institute of Bioregulation, Kyushu University, Fukuoka, Japan.
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Inoue
authors.affiliation: Division of Molecular and Clinical Genetics, Medical Institute of Bioregulation, Kyushu University, Fukuoka, Japan.
authors.forename: Tomotoshi
authors.initials: T
authors.lastname: Marumoto
authors.affiliation: Division of Molecular and Clinical Genetics, Medical Institute of Bioregulation, Kyushu University, Fukuoka, Japan.
authors.forename: Atsushi
authors.initials: A
authors.lastname: Takahashi
authors.affiliation: Department of Advanced Cell and Molecular Therapy, Kyushu University Hospital, Fukuoka, Japan.
authors.forename: Toshihiko
authors.initials: T
authors.lastname: Okazaki
authors.affiliation: Department of Immunology, Juntendo University School of Medicine, Tokyo, Japan.
authors.forename: Kazuyoshi
authors.initials: K
authors.lastname: Takeda
authors.affiliation: Department of Radiology, Kyushu University Hospital, Fukuoka, Japan.
authors.forename: Masakazu
authors.initials: M
authors.lastname: Hirakawa
authors.affiliation: Department of Pathology, Kyushu University, Fukuoka, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Fujii
authors.affiliation: Department of Pathology, Kyushu University, Fukuoka, Japan.
authors.forename: Shinji
authors.initials: S
authors.lastname: Okano
authors.affiliation: Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
authors.forename: Masaru
authors.initials: M
authors.lastname: Morita
authors.affiliation: Department of Medicine and Biosystemic Science, Kyushu University Graduate School of Medical Sciences, Fukuoka, Japan.
authors.forename: Eishi
authors.initials: E
authors.lastname: Baba
authors.affiliation: Department of Surgery and Oncology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Mizumoto
authors.affiliation: Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
authors.forename: Yoshihiko
authors.initials: Y
authors.lastname: Maehara
authors.affiliation: Department of Surgery and Oncology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
authors.forename: Masao
authors.initials: M
authors.lastname: Tanaka
authors.affiliation: Department of Medicine and Biosystemic Science, Kyushu University Graduate School of Medical Sciences, Fukuoka, Japan.
authors.forename: Koichi
authors.initials: K
authors.lastname: Akashi
authors.affiliation: Institute of Diseases of Chest, Kyushu University, Fukuoka, Japan.
authors.forename: Yoichi
authors.initials: Y
authors.lastname: Nakanishi
authors.affiliation: Human Genome Center, Institute of Medical Science, University of Tokyo, Tokyo, Japan.
authors.forename: Koji
authors.initials: K
authors.lastname: Yoshida
authors.affiliation: Human Genome Center, Institute of Medical Science, University of Tokyo, Tokyo, Japan.
authors.forename: Takuya
authors.initials: T
authors.lastname: Tsunoda
authors.affiliation: Division of Oncology, Hematology and Infectious Diseases, Department of Internal Medicine, Fukuoka University, Fukuoka, Japan.
authors.forename: Kazuo
authors.initials: K
authors.lastname: Tamura
authors.affiliation: Human Genome Center, Institute of Medical Science, University of Tokyo, Tokyo, Japan.
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Nakamura
authors.affiliation: Department of Advanced Cell and Molecular Therapy, Kyushu University Hospital, Fukuoka, Japan; Division of Molecular and Clinical Genetics, Medical Institute of Bioregulation, Kyushu University, Fukuoka, Japan. Electronic address: k-tani@ims.u-tokyo.ac.jp.
authors.forename: Kenzaburo
authors.initials: K
authors.lastname: Tani
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000276:immunology / Q000627:therapeutic use*; D019496:Cancer Vaccines / Q000008:administration & dosage / Q000009:adverse effects / Q000276:immunology*; D015179:Colorectal Neoplasms / Q000188:drug therapy / Q000235:genetics / Q000276:immunology; D003520:Cyclophosphamide / Q000008:administration & dosage / Q000009:adverse effects / Q000276:immunology*; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D000939:Epitopes / Q000008:administration & dosage / Q000276:immunology; D005260:Female; D059871:HLA-A24 Antigen / Q000235:genetics / Q000276:immunology; D006801:Humans; D053208:Kaplan-Meier Estimate; D007970:Leukopenia / Q000139:chemically induced; D008175:Lung Neoplasms / Q000188:drug therapy / Q000235:genetics / Q000276:immunology; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000276:immunology*; D010455:Peptides / Q000008:administration & dosage / Q000276:immunology; D013274:Stomach Neoplasms / Q000188:drug therapy / Q000235:genetics / Q000276:immunology; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D016896:Treatment Outcome; D022223:Vaccines, Subunit / Q000008:administration & dosage / Q000009:adverse effects / Q000276:immunology*
chemical_list: D019496:Cancer Vaccines; D000939:Epitopes; C438506:HLA-A*24:02 antigen; D059871:HLA-A24 Antigen; D010455:Peptides; D022223:Vaccines, Subunit; D003520:Cyclophosphamide
keywords: Cyclophosphamide; Five-peptide cancer vaccine; Regulatory T cells; Translational research