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 N.J. and Radford, Kristen J. (2012) Human kallikrein 4 signal peptide induces cytotoxic T cell responses in healthy donors and prostate cancer patients. Cancer Immunology, Immunotherapy, 61 2: 169-179. doi:10.1007/s00262-011-1095-2

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Author Wilkinson, Ray
Woods, Katherine
D’Rozario, Rachael
Prue, Rebecca
Vari, Frank
Hardy, Melinda Y.
Dong, Ying
Clements, Judith A.
Hart, Derek N.J.
Radford, Kristen J.
Title Human kallikrein 4 signal peptide induces cytotoxic T cell responses in healthy donors and prostate cancer patients
Journal name Cancer Immunology, Immunotherapy   Check publisher's open access policy
ISSN 0340-7004
1432-0851
Publication date 2012-02
Year available 2011
Sub-type Critical review of research, literature review, critical commentary
DOI 10.1007/s00262-011-1095-2
Open Access Status File (Author Post-print)
Volume 61
Issue 2
Start page 169
End page 179
Total pages 11
Place of publication Heidelberg, Germany
Publisher Springer
Collection year 2012
Language eng
Formatted abstract
Immunotherapy is a promising new treatment for patients with advanced prostate and ovarian cancer, but its application is limited by the Immunotherapy 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.
Keyword Cytotoxic T cells
Immunotherapy
Kallikrein
Prostate cancer
Tumor antigen
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ
Additional Notes Published online: 27 August 2011.

Document type: Journal Article
Sub-type: Critical review of research, literature review, critical commentary
Collections: Official 2012 Collection
School of Medicine Publications
 
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Citation counts: TR Web of Science Citation Count  Cited 10 times in Thomson Reuters Web of Science Article | Citations
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Created: Tue, 27 Sep 2011, 13:56:20 EST by Matthew Lamb on behalf of School of Medicine