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Protective immunosurveillance and therapeutic antitumor activity of gammadelta T cells demonstrated in a mouse model of prostate cancer.

Publication ,  Journal Article
Liu, Z; Eltoum, I-EA; Guo, B; Beck, BH; Cloud, GA; Lopez, RD
Published in: J Immunol
May 1, 2008

In contrast to Ag-specific alphabeta T cells, gammadelta T cells can kill malignantly transformed cells in a manner that does not require the recognition of tumor-specific Ags. Although such observations have contributed to the emerging view that gammadelta T cells provide protective innate immunosurveillance against certain malignancies, particularly those of epithelial origin, they also provide a rationale for developing novel clinical approaches to exploit the innate antitumor properties of gammadelta T cells for the treatment of cancer. Using TRAMP, a transgenic mouse model of prostate cancer, proof-of-concept studies were performed to first establish that gammadelta T cells can indeed provide protective immunosurveillance against spontaneously arising mouse prostate cancer. TRAMP mice, which predictably develop prostate adenocarcinoma, were backcrossed with gammadelta T cell-deficient mice (TCRdelta(-/-) mice) yielding TRAMP x TCRdelta(-/-) mice, a proportion of which developed more extensive disease compared with control TRAMP mice. By extension, these findings were then used as a rationale for developing an adoptive immunotherapy model for treating prostate cancer. Using TRAMP-C2 cells derived from TRAMP mice (C57BL/6 genetic background), disease was first established in otherwise healthy wild-type C57BL/6 mice. In models of localized and disseminated disease, tumor-bearing mice treated i.v. with supraphysiological numbers of syngeneic gammadelta T cells (C57BL/6-derived) developed measurably less disease compared with untreated mice. Disease-bearing mice treated i.v. with gammadelta T cells also displayed superior survival compared with untreated mice. These findings provide a biological rationale for clinical trials designed to adoptively transfer ex vivo expanded autologous gammadelta T cells for the treatment of prostate cancer.

Duke Scholars

Published In

J Immunol

DOI

ISSN

0022-1767

Publication Date

May 1, 2008

Volume

180

Issue

9

Start / End Page

6044 / 6053

Location

United States

Related Subject Headings

  • Transplantation, Isogeneic
  • T-Lymphocytes
  • Receptors, Antigen, T-Cell, gamma-delta
  • Receptors, Antigen, T-Cell, alpha-beta
  • Prostatic Neoplasms
  • Neoplasms, Experimental
  • Mice, Transgenic
  • Mice
  • Male
  • Lymphocyte Transfusion
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Liu, Z., Eltoum, I.-E., Guo, B., Beck, B. H., Cloud, G. A., & Lopez, R. D. (2008). Protective immunosurveillance and therapeutic antitumor activity of gammadelta T cells demonstrated in a mouse model of prostate cancer. J Immunol, 180(9), 6044–6053. https://doi.org/10.4049/jimmunol.180.9.6044
Liu, Zhiyong, Isam-Eldin A. Eltoum, Ben Guo, Benjamin H. Beck, Gretchen A. Cloud, and Richard D. Lopez. “Protective immunosurveillance and therapeutic antitumor activity of gammadelta T cells demonstrated in a mouse model of prostate cancer.J Immunol 180, no. 9 (May 1, 2008): 6044–53. https://doi.org/10.4049/jimmunol.180.9.6044.
Liu Z, Eltoum I-EA, Guo B, Beck BH, Cloud GA, Lopez RD. Protective immunosurveillance and therapeutic antitumor activity of gammadelta T cells demonstrated in a mouse model of prostate cancer. J Immunol. 2008 May 1;180(9):6044–53.
Liu, Zhiyong, et al. “Protective immunosurveillance and therapeutic antitumor activity of gammadelta T cells demonstrated in a mouse model of prostate cancer.J Immunol, vol. 180, no. 9, May 2008, pp. 6044–53. Pubmed, doi:10.4049/jimmunol.180.9.6044.
Liu Z, Eltoum I-EA, Guo B, Beck BH, Cloud GA, Lopez RD. Protective immunosurveillance and therapeutic antitumor activity of gammadelta T cells demonstrated in a mouse model of prostate cancer. J Immunol. 2008 May 1;180(9):6044–6053.

Published In

J Immunol

DOI

ISSN

0022-1767

Publication Date

May 1, 2008

Volume

180

Issue

9

Start / End Page

6044 / 6053

Location

United States

Related Subject Headings

  • Transplantation, Isogeneic
  • T-Lymphocytes
  • Receptors, Antigen, T-Cell, gamma-delta
  • Receptors, Antigen, T-Cell, alpha-beta
  • Prostatic Neoplasms
  • Neoplasms, Experimental
  • Mice, Transgenic
  • Mice
  • Male
  • Lymphocyte Transfusion