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

Wilkinson, Ray , Woods, Katherine , D'Rozario, Rachael , Prue, Rebecca , Vari, Frank , Hardy, Melinda Y , Dong, Ying, Clements, Judith A., Hart, Derek NJ , & Radford, Kirsten J (2012) Human Kallikrein 4 signal peptide induces cytotoxic T cell responses in healthy donors and prostate cancer patients. Cancer Immunology Immunotherapy, 61(2), pp. 169-179.

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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-A0201-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-A0201+ KLK4 + cell lines and KLK4 mRNA-transfected monocyte-derived dendritic cells. CTL specific for the HLA-A0201-restricted KLK4 peptide were more readily expanded to a higher frequency in vitro compared to the known HLA-A0201-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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2 citations in Web of Science®

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ID Code: 54766
Item Type: Journal Article
Keywords: kalikrein, Prostate Cancer, immunotherapy, tumor antigen, cytotoxic T cells
DOI: 10.1007/s00262-011-1095-2
ISSN: 0340-7004
Subjects: Australian and New Zealand Standard Research Classification > MEDICAL AND HEALTH SCIENCES (110000) > IMMUNOLOGY (110700) > Cellular Immunology (110704)
Australian and New Zealand Standard Research Classification > MEDICAL AND HEALTH SCIENCES (110000) > ONCOLOGY AND CARCINOGENESIS (111200) > Cancer Cell Biology (111201)
Australian and New Zealand Standard Research Classification > MEDICAL AND HEALTH SCIENCES (110000) > ONCOLOGY AND CARCINOGENESIS (111200) > Cancer Therapy (excl. Chemotherapy and Radiation Therapy) (111204)
Divisions: Current > Schools > School of Biomedical Sciences
Current > QUT Faculties and Divisions > Faculty of Health
Current > Institutes > Institute of Health and Biomedical Innovation
Copyright Owner: Copyright 2012 Springer
Deposited On: 21 Nov 2012 12:07
Last Modified: 21 Nov 2012 12:07

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