Phase I clinical trial of multiple-peptide vaccination for patients with advanced biliary tract cancer
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RESEARCH
Open Access
Phase I clinical trial of multiple-peptide vaccination for patients with advanced biliary tract cancer Atsushi Aruga1,2*, Nobuhiro Takeshita1, Yoshihito Kotera1, Ryuji Okuyama1, Norimasa Matsushita1, Takehiro Ohta1, Kazuyoshi Takeda3 and Masakazu Yamamoto1
Abstract 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). Keywords: Cancer vaccine, Peptide vaccine, Immunotherapy, Biliary tract cancer
Background Biliary tract cancer (BTC) is not a common disease worldwide, but is prevalent in East Asia and Latin America. The occurrence rate is gradually increasing and there is a high mortality rate because most cases of BTC are not diagnosed until advanced and inoperable. At this time, very few standard treatments have been established for BTC [1,2], and thus development of new treatment modalities is urgently needed. Recently, cancer vaccines using synthetic peptides have been undergoing development throughout the world, and some of them have already been shown to be safe and effective [3-12]. We have previously reported that cancer peptide vaccines are capable of inducing * Correspondence: [email protected] 1 Department of Gastroenterological Surgery, Tokyo Women's Medical University, 8-1 Kawada-cho, Shinjuku-ku, Tokyo 162-8666, Japan 2 Institute of Advanced Biomedical Engineering and Science, Tokyo Women's Medical University, 8-1 Kawada-cho, Shinjuku-ku, Tokyo 162-8666, Japan Full list of author information is available at the end of the article
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