Multicenter, phase II clinical trial of cancer vaccination for advanced esophageal cancer with three peptides derived from novel cancer-testis antigens

Journal of Translational Medicine

Research

Yasunori Akutsu¹  Hisahiro Matsubara¹  Kazuyoshi Takeda²  Kota Okinaka³  Hisae Iinuma³  Ryoji Fukushima³  Yasuto Uchikado⁴  Shoji Natsugoe⁴  Naoko Hayashi⁵  Hideo Baba⁵  Tsuyoshi Noguchi⁶  Seigou Kitano⁶  Hiroaki Tanaka⁷  Masaichi Ohira⁷  Hideki Fujii⁸  Koji Kono⁹  Yusuke Nakamura^1,10  Takuya Tsunoda^1,10  Koji Yoshida^1,10 

[1] Department of Frontier Surgery, Graduate School of Medicine, Chiba University, Chiba, Japan;Department of Immunology, Juntendo University School of Medicine, Juntendo, Japan;Department of Surgery, Teikyo University, Teikyo, Japan;Department of digestive surgery, Kagoshima University, Kagoshima, Japan;Department of gastroenterological surgery, Kumamoto University, Kumamoto, Japan;Department of gastroenterological surgery, Oita University, Oita, Japan;First Department of Surgery, Osaka City University, Osaka, Japan;First Department of Surgery, University of Yamanashi, Yamanashi, Japan;First Department of Surgery, University of Yamanashi, Yamanashi, Japan;Department of Surgery, National University of Singapore, Level 8, NUHS Tower Block, NUHS 1E Kent Ridge Road, 119228, Singapore, Singapore;Laboratory of Molecular Medicine, Human Genome Center, Institute of Medical Science, the University of Tokyo, Tokyo, Japan;

关键词: Cancer vaccine;    Esophageal cancer;    Phase II clinical trial;    CTL;    Peptide vaccine;   

DOI  :  10.1186/1479-5876-10-141

 received in 2012-04-15, accepted in 2012-07-09,  发布年份 2012

来源: Springer

【 摘 要 】

BackgroundSince a phase I clinical trial using three HLA-A24-binding peptides from TTK protein kinase (TTK), lymphocyte antigen-6 complex locus K (LY6K), and insulin-like growth factor-II mRNA binding protein-3 (IMP3) had been shown to be promising for esophageal squamous cell carcinoma (ESCC), we further performed a multicenter, non-randomized phase II clinical trial.Patients and methodsSixty ESCC patients were enrolled to evaluate OS, PFS, immunological response employing ELISPOT and pentamer assays. Each of the three peptides was administered with IFA weekly. All patients received the vaccination without knowing an HLA-A type, and the HLA types were key-opened at the analysis point. Hence, the endpoints were set to evaluate differences between HLA-A*2402-positive (24(+)) and -negative (24(−)) groups.ResultsThe OS in the 24 (+) group (n = 35) tended to be better than that in the 24(−) group (n = 25) (MST 4.6 vs. 2.6 month, respectively, p = 0.121), although the difference was not statistically significant. However, the PFS in the 24(+) group was significantly better than that in the 24(−) group (p = 0.032). In the 24(+) group, ELISPOT assay indicated that the LY6K-, TTK-, and IMP3-specific CTL responses were observed after the vaccination in 63%, 45%, and 60% of the 24(+) group, respectively. The patients having LY6K-, TTK-, and IMP3-specific CTL responses revealed the better OS than those not having CTL induction, respectively. The patients showing the CTL induction for multiple peptides have better clinical responses.ConclusionsThe immune response induced by the vaccination could make the prognosis better for advanced ESCC patients.Trial registrationClinicalTrials.gov, number NCT00995358

【 授权许可】

CC BY   
© Kono et al.; licensee BioMed Central Ltd. 2012