Human kallikrein 4 signal peptide induces cytotoxic T cell responses in healthy donors and prostate cancer patients

Cancer Immunol Immunother. 2012 Feb;61(2):169-179. doi: 10.1007/s00262-011-1095-2. Epub 2011 Aug 27.


Immunotherapy is a promising new treatment for patients with advanced prostate and ovarian cancer, but its application is limited by the lack of suitable target antigens that are recognized by CD8+ cytotoxic T lymphocytes (CTL). Human kallikrein 4 (KLK4) is a member of the kallikrein family of serine proteases that is significantly overexpressed in malignant versus healthy prostate and ovarian tissue, making it an attractive target for immunotherapy. We identified a naturally processed, HLA-A*0201-restricted peptide epitope within the signal sequence region of KLK4 that induced CTL responses in vitro in most healthy donors and prostate cancer patients tested. These CTL lysed HLA-A*0201+ KLK4 + cell lines and KLK4 mRNA-transfected monocyte-derived dendritic cells. CTL specific for the HLA-A*0201-restricted KLK4 peptide were more readily expanded to a higher frequency in vitro compared to the known HLA-A*0201-restricted epitopes from prostate cancer antigens; prostate-specific antigen (PSA), prostate-specific membrane antigen (PSMA) and prostatic acid phosphatase (PAP). These data demonstrate that KLK4 is an immunogenic molecule capable of inducing CTL responses and identify it as an attractive target for prostate and ovarian cancer immunotherapy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Antigens, Neoplasm / immunology
  • Antigens, Neoplasm / metabolism*
  • Cell Proliferation
  • Computational Biology
  • Dendritic Cells / immunology
  • Female
  • HLA-A2 Antigen / metabolism
  • Humans
  • Immunodominant Epitopes / genetics
  • Kallikreins / immunology
  • Kallikreins / metabolism*
  • Lymphocyte Activation
  • Male
  • Middle Aged
  • Peptide Fragments / immunology
  • Peptide Fragments / metabolism*
  • Prostatic Neoplasms / immunology*
  • Prostatic Neoplasms / pathology
  • Protein Sorting Signals / genetics
  • T-Lymphocytes, Cytotoxic / immunology
  • T-Lymphocytes, Cytotoxic / metabolism*
  • T-Lymphocytes, Cytotoxic / pathology


  • Antigens, Neoplasm
  • HLA-A*02:01 antigen
  • HLA-A2 Antigen
  • Immunodominant Epitopes
  • Peptide Fragments
  • Protein Sorting Signals
  • Kallikreins
  • kallikrein 4