title: Human kallikrein 4 signal peptide induces cytotoxic T cell responses in healthy donors and prostate cancer patients.
abstract: 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.
authors.affiliation: Dendritic Cell Program, Mater Medical Research Institute, Level 3 Aubigny Place, South Brisbane, QLD, 4101, Australia.|Renal Research Laboratory, Queensland Health/Queensland Institute of Medical Research, Brisbane, QLD, Australia.
authors.forename: Ray
authors.initials: R
authors.lastname: Wilkinson
authors.affiliation: Dendritic Cell Program, Mater Medical Research Institute, Level 3 Aubigny Place, South Brisbane, QLD, 4101, Australia.
authors.forename: Katherine
authors.initials: K
authors.lastname: Woods
authors.affiliation: Dendritic Cell Program, Mater Medical Research Institute, Level 3 Aubigny Place, South Brisbane, QLD, 4101, Australia.
authors.forename: Rachael
authors.initials: R
authors.lastname: D'Rozario
authors.affiliation: Dendritic Cell Program, Mater Medical Research Institute, Level 3 Aubigny Place, South Brisbane, QLD, 4101, Australia.
authors.forename: Rebecca
authors.initials: R
authors.lastname: Prue
authors.affiliation: Dendritic Cell Program, Mater Medical Research Institute, Level 3 Aubigny Place, South Brisbane, QLD, 4101, Australia.|Clinical Immunohematology, Queensland Institute of Medical Research, Brisbane, QLD, Australia.
authors.forename: Frank
authors.initials: F
authors.lastname: Vari
authors.affiliation: Dendritic Cell Program, Mater Medical Research Institute, Level 3 Aubigny Place, South Brisbane, QLD, 4101, Australia.
authors.forename: Melinda Y
authors.initials: MY
authors.lastname: Hardy
authors.affiliation: Institute of Health and Biomedical Innovation and Australian Prostate Cancer Research Centre-Queensland, Queensland University of Technology, Brisbane, QLD, Australia.
authors.forename: Ying
authors.initials: Y
authors.lastname: Dong
authors.affiliation: Institute of Health and Biomedical Innovation and Australian Prostate Cancer Research Centre-Queensland, Queensland University of Technology, Brisbane, QLD, Australia.
authors.forename: Judith A
authors.initials: JA
authors.lastname: Clements
authors.affiliation: Dendritic Cell Program, Mater Medical Research Institute, Level 3 Aubigny Place, South Brisbane, QLD, 4101, Australia.|Dendritic Cell Biology and Therapeutics, ANZAC Research Institute, Concord Hospital, Hospital Road, Sydney, NSW, 2139, Australia.
authors.forename: Derek N J
authors.initials: DNJ
authors.lastname: Hart
authors.affiliation: Dendritic Cell Program, Mater Medical Research Institute, Level 3 Aubigny Place, South Brisbane, QLD, 4101, Australia. kradford@mmri.mater.org.au.
authors.forename: Kristen J
authors.initials: KJ
authors.lastname: Radford
mesh_terms: D000328:Adult; D000368:Aged; D000951:Antigens, Neoplasm / Q000276:immunology / Q000378:metabolism*; D049109:Cell Proliferation; D019295:Computational Biology; D003713:Dendritic Cells / Q000276:immunology; D005260:Female; D015789:HLA-A2 Antigen / Q000378:metabolism; D006801:Humans; D016056:Immunodominant Epitopes / Q000235:genetics; D007610:Kallikreins / Q000276:immunology / Q000378:metabolism*; D008213:Lymphocyte Activation; D008297:Male; D008875:Middle Aged; D010446:Peptide Fragments / Q000276:immunology / Q000378:metabolism*; D011471:Prostatic Neoplasms / Q000276:immunology* / Q000473:pathology; D021382:Protein Sorting Signals / Q000235:genetics; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology / Q000378:metabolism* / Q000473:pathology
chemical_list: D000951:Antigens, Neoplasm; C435939:HLA-A*02:01 antigen; D015789:HLA-A2 Antigen; D016056:Immunodominant Epitopes; D010446:Peptide Fragments; D021382:Protein Sorting Signals; D007610:Kallikreins; C120801:kallikrein 4