Phase I clinical trial of vaccination with URLC10-derived peptide for patients with advanced esophageal cancer |
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Authors: | Hajime Ishikawa Motohiro Imano Osamu Shiraishi Atsushi Yasuda Ying-Feng Peng Masayuki Shinkai Takushi Yasuda Haruhiko Imamoto Kazuyoshi Takeda Hitoshi Shiozaki |
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Institution: | 1. Department of Surgery, Kinki University, 377-2 Ohno-higasi, Osaka-sayama, Osaka, 589-8511, Japan 2. Department of Immunology, Juntendo University School of Medicine, Hongo 2-1-1, Bunkyo-ku, Tokyo, 113-8421, Japan
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Abstract: | Background Up-regulated gene in lung cancer 10 (URLC10), confirmed to be lymphocyte antigen 6 complex locus K and defined as an oncoantigen, has been identified as a tumor-associated antigen by systematic analysis of expression levels of thousands of genes in lung cancer tissues and esophageal squamous cell carcinoma tissues, which were compared with those of normal human tissues by use of cDNA microarray analysis. Human leukocyte antigen (HLA)-A*2402-positive dendritic cells pulsed with URLC10-derived epitope peptide induced CD8+ cytotoxic T lymphocytes to exert specific cytotoxicity against the HLA-A*2402-positive URLC10-expressing esophageal carcinoma cell lines. Methods In a phase I clinical trial we evaluated the safety and immunogenicity of a URLC10-177 peptide vaccine emulsified with Montanide ISA51 for patients with unresectable advanced esophageal cancer. One milligram of URLC10-177 peptide in 1 mL sterile saline was emulsified with 1 mL incomplete Freund’s adjuvant and administered subcutaneously to the inguinal region or axilla of the patients. One course of treatment comprised four vaccinations, which were performed every week in the first and second treatment courses and subsequently every 2 weeks after the first vaccination in the third treatment course. Results Redness and induration of the skin were the only adverse events at the injection site and were believed to be a delayed-type hypersensitivity (DTH) reaction against the peptide vaccine. A URLC10-177-specific immune reaction in the enzyme-linked immunospot assay was detected in three of four DTH-positive patients (75 %) and in one of three DTH-negative patients (33 %). Furthermore, patients who had a DTH reaction seemed to survive longer than those who had no DTH reaction. Conclusion URLC10-177 peptide/Montanide vaccine therapy was well tolerated and induced a URLC10-177 peptide-specific immune response. Therapeutic URLC10-177 peptide vaccination is expected to have clinical benefit in prolonging the survival of patients with unresectable advanced esophageal cancer. |
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