Cancer peptide vaccine therapy developed from oncoantigens identified through genome-wide expression profile analysis for bladder cancer

Jpn J Clin Oncol. 2012 Jul;42(7):591-600. doi: 10.1093/jjco/hys069. Epub 2012 May 25.

Abstract

Objective: The field of cancer vaccine therapy is currently expected to become the fourth option in the treatment of cancer after surgery, chemotherapy and radiation therapy. We developed a novel cancer peptide vaccine therapy for bladder cancer through a genome-wide expression profile analysis.

Methods: Among a number of oncoproteins that are transactivated in cancer cells, we focused on M phase phosphoprotein 1 and DEP domain containing 1, both of which are cancer-testis antigens playing critical roles in the growth of bladder cancer cells, as candidate molecules for the development of drugs for bladder cancer. In an attempt to identify the peptide epitope from these oncoantigens, we conducted a clinical trial using these peptides for patients with advanced bladder cancer.

Results: We identified HLA-A24-restricted peptide epitopes corresponding to parts of M phase phosphoprotein 1 and DEP domain containing 1 proteins, which could induce peptide-specific cytotoxic T lymphocytes. Using these peptides, we found that M phase phosphoprotein 1- and DEP domain containing 1-derived peptide vaccines could be well tolerated without any serious adverse events, and effectively induced peptide-specific cytotoxic T lymphocytes in vivo.

Conclusions: The novel approach adopted in the treatment with peptide vaccines is considered to be a promising therapy for bladder cancer.

Publication types

  • Clinical Trial

MeSH terms

  • Adjuvants, Immunologic / administration & dosage
  • Adult
  • Aged
  • Antigens, Neoplasm / immunology*
  • Cancer Vaccines / administration & dosage
  • Cancer Vaccines / immunology
  • Cancer Vaccines / therapeutic use*
  • DNA, Complementary / analysis
  • DNA, Neoplasm / analysis
  • Dendritic Cells*
  • Drug Administration Schedule
  • Female
  • Freund's Adjuvant / administration & dosage
  • Gene Expression Profiling
  • Genome-Wide Association Study
  • Humans
  • Immunohistochemistry
  • Kinesins / administration & dosage
  • Kinesins / immunology*
  • Kinesins / therapeutic use*
  • Laser Capture Microdissection
  • Male
  • Middle Aged
  • Peptides
  • Protein Array Analysis
  • Receptor-Like Protein Tyrosine Phosphatases, Class 3 / administration & dosage
  • Receptor-Like Protein Tyrosine Phosphatases, Class 3 / immunology
  • Receptor-Like Protein Tyrosine Phosphatases, Class 3 / therapeutic use*
  • T-Lymphocytes, Cytotoxic / drug effects
  • T-Lymphocytes, Cytotoxic / immunology*
  • Treatment Outcome
  • Urinary Bladder Neoplasms / drug therapy*
  • Urinary Bladder Neoplasms / immunology*
  • Urinary Bladder Neoplasms / pathology
  • Urinary Bladder Neoplasms / surgery

Substances

  • Adjuvants, Immunologic
  • Antigens, Neoplasm
  • Cancer Vaccines
  • DEPDC1-294 peptide
  • DNA, Complementary
  • DNA, Neoplasm
  • MPHOSPH1-278 peptide
  • Peptides
  • Freund's Adjuvant
  • PTPRJ protein, human
  • Receptor-Like Protein Tyrosine Phosphatases, Class 3
  • KIF20B protein, human
  • Kinesins