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Phase I clinical trial of vaccination with URLC10-derived peptide for patients with advanced esophageal cancer

An Erratum to this article was published on 01 June 2012

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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Acknowledgments

The authors would like to thank Professor Yusuke Nakamura, Dr Takuya Tsunoda, Dr Koji Yoshida, Mr Ryuji Osawa, and Ms Sachiko Yoshimura, Laboratory of Molecular Medicine, Human Genome Center, Institute of Medical Science, The University of Tokyo, for their excellent advice and cooperation and for providing the peptides.

Conflict of interest

The authors declare that they have no conflict of interest.

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Correspondence to Hajime Ishikawa.

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Ishikawa, H., Imano, M., Shiraishi, O. et al. Phase I clinical trial of vaccination with URLC10-derived peptide for patients with advanced esophageal cancer. Esophagus 9, 105–112 (2012). https://doi.org/10.1007/s10388-012-0315-y

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Keywords

  • Esophageal cancer
  • URLC10
  • LY6K protein
  • Peptide vaccine
  • Oncoantigen