Phase I clinical study of multiple epitope peptide vaccine combined with chemoradiation therapy in esophageal cancer patients

Journal of Translational Medicine

Research

Kazuyoshi Takeda¹  Masahiro Horikawa²  Kota Okinaga²  Hisae Iinuma²  Noriyuki Matsutani²  Junko Tamura²  Yoshibumi Ikeda²  Ryoji Fukushima²  Tsuyoshi Inaba²  Taisuke Inoue²  Tadashi Ikeda²  Etsushi Ogawa²  Takuya Tsunoda³  Koji Yoshida³  Yusuke Nakamura⁴ 

[1] Department of Immunology, Juntendo University School of Medicine, Tokyo, Japan;Department of Surgery, Teikyo University School of Medicine, Tokyo, Japan;Laboratory of Molecular Medicine, Human Genome Center, Institute of Medical Science, University of Tokyo, Tokyo, Japan;OncoTherapy Science Incorporation, Research and Development Division, Kanagawa, Japan;Laboratory of Molecular Medicine, Human Genome Center, Institute of Medical Science, University of Tokyo, Tokyo, Japan;The University of Chicago, Chicago, IL, USA;

关键词: Cancer vaccine;    Chemoradiation therapy;    Esophageal cancer;    CTL;    Phase I clinical trial;   

DOI  :  10.1186/1479-5876-12-84

 received in 2013-11-21, accepted in 2014-03-13,  发布年份 2014

来源: Springer

【 摘 要 】

BackgroundChemoradiation therapy (CRT) has been widely used for unresectable esophageal squamous cell carcinoma (ESCC) patients. However, many patients develop local recurrence after CRT. In this study, we hypothesized that the immunotherapy by peptide vaccine may be effective for the eradication of minimal residual cancer cells after CRT. This study was conducted as a phase I clinical trial of multiple-peptide vaccine therapy combined with CRT on patients with unresectable ESCC.Patients and methodsHLA-A*2402 positive 11 unresectable chemo-naïve ESCC patients were treated by HLA-A*2402-restricted multi-peptide vaccine combined with CRT. The peptide vaccine included the 5 peptides as follows; TTK protein kinase (TTK), up-regulated lung cancer 10 (URLC10), insulin-like growth factor–II mRNA binding protein 3 (KOC1), vascular endothelial growth factor receptor 1 (VEGFR1) and 2 (VEGFR2). CRT consisted of radiotherapy (60 Gy) with concurrent cisplatin (40 mg/m2) and 5-fluorouracil (400 mg/m2). Peptide vaccines mixed with incomplete Freund’s adjuvant were injected subcutaneously once a week on at least 8 occasions combined with CRT.ResultsVaccination with CRT therapy was well-tolerated, and no severe adverse effects were observed. In the case of grade 3 toxicities, leucopenia, neutropenia, anemia and thrombocutopenia occurred in 54.5%, 27.3%, 27.3% and 9.1% of patients, respectively. Grade 1 local skin reactions in the injection sites of vaccination were observed in 81.8% of patients. The expressions of HLA class I, URLC10, TTK, KOC1, VEGFR1 and VEGFR2 antigens were observed in the tumor tissues of all patients. All patients showed peptide-specific cytotoxic T lymphocytes responses in at least one of the 5 kinds of peptide antigens during the vaccination. Six cases of complete response (CR) and 5 cases of progressive disease (PD) were observed after the 8th vaccination. The 4 CR patients who continued the peptide vaccination experienced long consistent CR for 2.0, 2.9 4.5 and 4.6 years.ConclusionsA combination therapy of multi-peptide vaccine with CRT can successfully be performed with satisfactory levels of safety, and application of this combination therapy may be an effective treatment for patients with unresectable ESCC.Trial registrationClinicalTrial.gov, number NCT00632333.

【 授权许可】

CC BY   
© Iinuma et al.; licensee BioMed Central Ltd. 2014