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Induction of hsp70-mediated Th17 autoimmunity can be exploited as immunotherapy for metastatic prostate cancer

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Kottke, T., Sanchez-Perez, L., Diaz, R. M., Thompson, J., Chong, H., Harrington, K., Calderwood, S. K., Pulido, J., Georgopoulos, N., Selby, P., Melcher, A., Vile, R. (2007) Induction of hsp70-mediated Th17 autoimmunity can be exploited as immunotherapy for metastatic prostate cancer. CANCER RESEARCH, 67 (24). pp. 11970-11979. ISSN 0008-5472

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A copy of the full text may be available at: http://cancerres.aacrjournals.org/cgi/content/full...

Abstract

A close connectivity between autoinumme and tumor rejection responses is known to exist in the case of melanoma immunotherapy. However, relatively little is known about self-antigens on other types of normal cells, their relation to the development of autoinumme disease, and their possible coexistence as potential tumor rejection antigens on associated tumors. In the current study, we induced inflammatory killing of normal prostate tissue in situ using a fusogenic membrane glycoprotein along with the immune adjuvant hsp70. We show here that, in the prostate, hsp70 induces interleukin (IL)-6, which triggers a CD4- and CD8-dependent progressive autoimmune reactivity, associated with IL-17 expression. This autoinumme response was also able to induce the rejection of established prostate tumors, but not other histologic types of tumors, growing elsewhere in the animal. These data show that the intimate connectivity between autoimmune and tumor rejection responses extends beyond the classic melanoma paradigm and may be clinically valuable for the treatment of established metastatic disease of the prostate.

Item Type: Article
Authors (ICR Faculty only): Harrington, Kevin
All Authors: Kottke, T., Sanchez-Perez, L., Diaz, R. M., Thompson, J., Chong, H., Harrington, K., Calderwood, S. K., Pulido, J., Georgopoulos, N., Selby, P., Melcher, A., Vile, R.
Uncontrolled Keywords: FUSOGENIC MEMBRANE GLYCOPROTEIN; REGULATORY T-CELLS; SHOCK-PROTEIN EXPRESSION; IN-VIVO; GENE-THERAPY; ANTIGEN DELIVERY; IMMUNE-RESPONSE; TUMOR-ANTIGENS; TGF-BETA; MELANOMA
Research teams: Clinical Units > Head & Neck Cancer Unit
ICR divisions > Cancer Biology > Targeted Therapy
ICR divisions > Radiotherapy and Imaging > Targeted Therapy
Depositing User: Users 10 not found.
Date Deposited: 20 Feb 2008 14:10
Last Modified: 10 Feb 2010 11:50
URI: http://publications.icr.ac.uk/id/eprint/5610

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