Human kallikrein 4 signal peptide induces cytotoxic T cell responses in healthy donors and prostate cancer patients |
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Authors: | Ray Wilkinson Katherine Woods Rachael D’Rozario Rebecca Prue Frank Vari Melinda Y Hardy Ying Dong Judith A Clements Derek N J Hart Kristen J Radford |
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Institution: | (1) Dendritic Cell Program, Mater Medical Research Institute, Level 3 Aubigny Place, South Brisbane, QLD, 4101, Australia;(2) Institute of Health and Biomedical Innovation and Australian Prostate Cancer Research Centre-Queensland, Queensland University of Technology, Brisbane, QLD, Australia;(3) Present address: Renal Research Laboratory, Queensland Health/Queensland Institute of Medical Research, Brisbane, QLD, Australia;(4) Present address: Clinical Immunohematology, Queensland Institute of Medical Research, Brisbane, QLD, Australia;(5) Present address: Dendritic Cell Biology and Therapeutics, ANZAC Research Institute, Concord Hospital, Hospital Road, Sydney, NSW, 2139, Australia |
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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. |
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