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

Yusuke Nakamura⁹  Takuya Tsunoda⁹  Koji Yoshida⁹  Kazuyoshi Takeda³  Seigou Kitano¹  Shoji Natsugoe⁷  Hideo Baba⁴  Masaichi Ohira^1,10  Hisahiro Matsubara²  Ryoji Fukushima⁶  Kota Okinaka⁶  Hideki Fujii⁸  Tsuyoshi Noguchi¹  Yasuto Uchikado⁷  Naoko Hayashi⁴  Hiroaki Tanaka^1,10  Yasunori Akutsu²  Hisae Iinuma⁶  Koji Kono⁵ 

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

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

Others  :  1205940
DOI  :  10.1186/1479-5876-10-141

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

【 摘 要 】

Background

Since 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 methods

Sixty 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.

Results

The 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.

Conclusions

The immune response induced by the vaccination could make the prognosis better for advanced ESCC patients.

Trial registration

ClinicalTrials.gov, number NCT00995358

【 授权许可】

   
2012 Kono et al.; licensee BioMed Central Ltd.

【 图 表 】

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