Phase I clinical trial of multiple-peptide vaccination for patients with advanced biliary tract cancer

Journal of Translational Medicine

Masakazu Yamamoto¹  Kazuyoshi Takeda²  Takehiro Ohta¹  Norimasa Matsushita¹  Ryuji Okuyama¹  Yoshihito Kotera¹  Nobuhiro Takeshita¹  Atsushi Aruga³ 

[1] Department of Gastroenterological Surgery, Tokyo Women's Medical University, 8-1 Kawada-cho, Shinjuku-ku, Tokyo 162-8666, Japan;Department of Immunology, Juntendo School of Medicine, 2-1-1 Hongo, Bunkyo-ku, Tokyo 113-8421, Japan;Institute of Advanced Biomedical Engineering and Science, Tokyo Women's Medical University, 8-1 Kawada-cho, Shinjuku-ku, Tokyo 162-8666, Japan

关键词: Biliary tract cancer;    Immunotherapy;    Peptide vaccine;    Cancer vaccine;   

Others  :  817750
DOI  :  10.1186/1479-5876-12-61

 received in 2013-09-26, accepted in 2014-03-04,  发布年份 2014

【 摘 要 】

Background

The prognosis of patients with advanced biliary tract cancer (BTC) is extremely poor and only a few standard treatments are available for this condition. We performed a phase I trial to investigate the safety, immune response and anti-tumor effect of vaccination with three peptides derived from cancer-testis antigens.

Methods

This study was conducted as a phase I trial. Nine patients with advanced BTC who had unresectable tumors and were refractory to standard chemotherapy were enrolled. Three HLA-A*2402 restricted epitope peptides-cell division cycle associated 1 (CDCA1), cadherin 3 (CDH3) and kinesin family member 20A (KIF20A)-were administered subcutaneously, and the adverse events and immune response were assessed. The clinical effects observed were the tumor response, progression-free survival (PFS) and overall survival (OS).

Results

The three-peptide vaccination was well-tolerated up to a dose of 3 mg per peptide (9 mg total). No grade 3 or 4 adverse events were observed after vaccination. Peptide-specific T cell immune responses were observed in all patients and stable disease was observed in 5 of 9 patients. The median PFS and OS were 3.4 and 9.7 months. The Grade 2 injection site reaction and continuous vaccination after PD judgment appeared to be prognostic of OS.

Conclusions

Multiple-peptide vaccination was well tolerated and induced peptide-specific T-cell responses.

Trial registration

This study was registered with the University Hospital Medical Information Network Clinical Trials Registry (UMIN-CTR000003229).

【 授权许可】

   
2014 Aruga et al.; licensee BioMed Central Ltd.

【 图 表 】

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