title: A phase I clinical trial of vaccination with KIF20A-derived peptide in combination with gemcitabine for patients with advanced pancreatic cancer.
abstract: KIF20A (RAB6KIFL) belongs to the kinesin superfamily of motor proteins, which play critical roles in the trafficking of molecules and organelles during the growth of pancreatic cancer. Immunotherapy using a previously identified epitope peptide for KIF20A is expected to improve clinical outcomes. A phase I clinical trial combining KIF20A-derived peptide with gemcitabine (GEM) was therefore conducted among patients with advanced pancreatic cancer who had received prior therapy such as chemotherapy and/or radiotherapy. GEM was administered at a dose of 1000 mg/m(2) on days 1, 8, and 15 in a 28-day cycle. The KIF20A-derived peptide was injected subcutaneously on a weekly basis in a dose-escalation manner (doses of 0.5, 1, and 3 mg/body; 3 patients/cohort). Safety and immunologic parameters were assessed. No severe adverse effects of grade 3 or higher related to KIF20A-derived peptide were observed. Of the 9 patients who completed at least one course of treatment, interferon-γ (IFN-γ)-producing cells were induced in 4 of 9 patients (P2, P3, P6, and P7), and IFN-γ-producing cells were increased in 4 of the 9 patients (P1, P5, P8, and P9). Four of the 9 patients achieved stable disease. The disease control rate was 44%. The median survival time after first vaccination was 173 days and 1-year survival rate was 11.1%. IFN-γ-producing cells were induced by the KIF20A-derived peptide vaccine at a high rate, even in combination with GEM. These results suggest that this combination therapy will be feasible and promising for the treatment of advanced pancreatic cancer.
authors: *Departments of Digestive Surgery and Surgical Oncology (Surgery II), Yamaguchi University Graduate School of Medicine, Yamaguchi †Department of Immunology, Juntendo University School of Medicine, Tokyo, Japan.
authors: Nobuaki
authors: N
authors: Suzuki
authors: Shoichi
authors: S
authors: Hazama
authors: Tomio
authors: T
authors: Ueno
authors: Hiroto
authors: H
authors: Matsui
authors: Yoshitaro
authors: Y
authors: Shindo
authors: Michihisa
authors: M
authors: Iida
authors: Kiyoshi
authors: K
authors: Yoshimura
authors: Shigefumi
authors: S
authors: Yoshino
authors: Kazuyoshi
authors: K
authors: Takeda
authors: Masaaki
authors: M
authors: Oka
mesh_terms: D000368:Aged; D000964:Antimetabolites, Antineoplastic / Q000009:adverse effects / Q000627:therapeutic use*; D019496:Cancer Vaccines / Q000008:administration & dosage / Q000009:adverse effects / Q000276:immunology*; D003131:Combined Modality Therapy; D003841:Deoxycytidine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D005260:Female; D006801:Humans; D016547:Kinesins / Q000737:chemistry / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D010190:Pancreatic Neoplasms / Q000276:immunology / Q000401:mortality / Q000473:pathology* / Q000628:therapy*; D010446:Peptide Fragments / Q000008:administration & dosage / Q000009:adverse effects / Q000276:immunology*; D016176:T-Lymphocyte Subsets / Q000276:immunology / Q000378:metabolism; D014057:Tomography, X-Ray Computed; D016896:Treatment Outcome; D022223:Vaccines, Subunit / Q000008:administration & dosage / Q000009:adverse effects / Q000276:immunology; D000093542:Gemcitabine
chemical_list: D000964:Antimetabolites, Antineoplastic; D019496:Cancer Vaccines; C410089:KIF20A protein, human; D010446:Peptide Fragments; D022223:Vaccines, Subunit; D003841:Deoxycytidine; D016547:Kinesins; D000093542:Gemcitabine