Phase I clinical trial of vaccination with LY6K-derived peptide in patients with advanced gastric cancer

Gastric Cancer. 2014 Jan;17(1):173-80. doi: 10.1007/s10120-013-0258-6. Epub 2013 Apr 24.

Abstract

Background: Lymphocyte antigen 6 complex locus K (LY6K) has been identified as a tumor-associated antigen in lung cancers and esophageal squamous cell carcinomas. The immunogenicity of LY6K-177 peptide vaccine therapy has been demonstrated in patients with advanced esophageal cancer. This study extends this treatment to gastric cancer.

Methods: LY6K expression in clinical samples obtained from gastric cancer patients was examined by immunochemistry. As a phase I clinical trial, the safety and immunogenicity of LY6K-177 peptide vaccine emulsified with Montanide ISA 51 was evaluated in six patients with unresectable advanced gastric cancer. LY6K-177 peptide (1 mg in 1 ml sterile saline) was emulsified with incomplete Freund's adjuvant (1 ml) and intracutaneously administered to the inguinal region or axilla. One treatment course comprised four vaccinations, performed weekly for the first and second treatment courses and biweekly for the third treatment course.

Results: LY6K expression was confirmed in 85 % of gastric cancer tissues. Induration and redness at the vaccination site (grade I), possibly a delayed-type hypersensitivity reaction, was observed in all patients; however, no systemic toxicology was identified in any patient throughout the observation period. Three of the six patients had stable disease, and a tumor contraction effect was observed in one patient.

Conclusions: LY6K was expressed in 85 % of observed gastric cancers. Vaccination with LY6K-177 peptide/Montanide ISA 51 appeared to be tolerated by advanced gastric cancer patients, and moreover anticancer efficacy was suggested. This trial was registered with ClinicalTrial.gov (no. NCT00845611).

Publication types

  • Clinical Trial, Phase I

MeSH terms

  • Aged
  • Antigens, Ly / analysis
  • Antigens, Ly / immunology*
  • Antigens, Ly / metabolism
  • Cancer Vaccines / adverse effects
  • Cancer Vaccines / therapeutic use*
  • Female
  • GPI-Linked Proteins / analysis
  • GPI-Linked Proteins / immunology
  • GPI-Linked Proteins / metabolism
  • Humans
  • Immunotherapy / methods
  • Male
  • Mannitol / analogs & derivatives
  • Mannitol / immunology
  • Middle Aged
  • Oleic Acids / immunology
  • Peptide Fragments / immunology
  • Stomach Neoplasms / immunology*
  • Stomach Neoplasms / pathology
  • Stomach Neoplasms / therapy*
  • Treatment Outcome
  • Vaccination*

Substances

  • Antigens, Ly
  • Cancer Vaccines
  • GPI-Linked Proteins
  • LY6K protein, human
  • Oleic Acids
  • Peptide Fragments
  • montanide ISA 51
  • Mannitol

Associated data

  • ClinicalTrials.gov/NCT00845611