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Vaccination against the forkhead family transcription factor Foxp3 enhances tumor immunity.

Publication ,  Journal Article
Nair, S; Boczkowski, D; Fassnacht, M; Pisetsky, D; Gilboa, E
Published in: Cancer Res
January 1, 2007

Depletion of CD4+CD25+ regulatory T cells (Treg) by treatment with alphaCD25 antibody synergizes with vaccination protocols to engender protective immunity in mice. The effectiveness of targeting CD25 to eliminate Treg is limited by the fact that CD25, the low-affinity interleukin-2 receptor, is up-regulated on conventional T cells. At present, foxp3 is the only product known to be exclusively expressed in Treg of mice. However, foxp3 is not expressed on the cell surface and hence cannot be targeted with antibodies. In this study, we tested the hypothesis that vaccination of mice against foxp3, a self-antigen expressed also in the thymus, is capable of stimulating foxp3-specific CTL that will cause the depletion of Treg and enhanced antitumor immunity. Vaccination of mice with foxp3 mRNA-transfected dendritic cells elicited a robust foxp3-specific CTL response and potentiated vaccine-induced protective immunity comparably with that of alphaCD25 antibody administration. In contrast to alphaCD25 antibody treatment, repeated foxp3 vaccination did not interfere with vaccine-induced protective immunity. Importantly, foxp3 vaccination led to the preferential depletion of foxp3-expressing Treg in the tumor but not in the periphery, whereas alphaCD25 antibody treatment led to depletion of Treg in both the tumor and the periphery. Targeting foxp3 by vaccination offers a specific and simpler protocol for the prolonged control of Treg that may be associated with reduced risk of autoimmunity, introducing an approach whereby specific depletion of cells is not limited to targeting products expressed on the cell surface.

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Published In

Cancer Res

DOI

ISSN

0008-5472

Publication Date

January 1, 2007

Volume

67

Issue

1

Start / End Page

371 / 380

Location

United States

Related Subject Headings

  • Vaccination
  • Transfection
  • T-Lymphocytes, Regulatory
  • RNA, Messenger
  • Oncology & Carcinogenesis
  • Mice, Inbred C57BL
  • Mice
  • Melanoma, Experimental
  • Interleukin-2 Receptor alpha Subunit
  • Immunotherapy, Adoptive
 

Citation

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Nair, S., Boczkowski, D., Fassnacht, M., Pisetsky, D., & Gilboa, E. (2007). Vaccination against the forkhead family transcription factor Foxp3 enhances tumor immunity. Cancer Res, 67(1), 371–380. https://doi.org/10.1158/0008-5472.CAN-06-2903
Nair, Smita, David Boczkowski, Martin Fassnacht, David Pisetsky, and Eli Gilboa. “Vaccination against the forkhead family transcription factor Foxp3 enhances tumor immunity.Cancer Res 67, no. 1 (January 1, 2007): 371–80. https://doi.org/10.1158/0008-5472.CAN-06-2903.
Nair S, Boczkowski D, Fassnacht M, Pisetsky D, Gilboa E. Vaccination against the forkhead family transcription factor Foxp3 enhances tumor immunity. Cancer Res. 2007 Jan 1;67(1):371–80.
Nair, Smita, et al. “Vaccination against the forkhead family transcription factor Foxp3 enhances tumor immunity.Cancer Res, vol. 67, no. 1, Jan. 2007, pp. 371–80. Pubmed, doi:10.1158/0008-5472.CAN-06-2903.
Nair S, Boczkowski D, Fassnacht M, Pisetsky D, Gilboa E. Vaccination against the forkhead family transcription factor Foxp3 enhances tumor immunity. Cancer Res. 2007 Jan 1;67(1):371–380.

Published In

Cancer Res

DOI

ISSN

0008-5472

Publication Date

January 1, 2007

Volume

67

Issue

1

Start / End Page

371 / 380

Location

United States

Related Subject Headings

  • Vaccination
  • Transfection
  • T-Lymphocytes, Regulatory
  • RNA, Messenger
  • Oncology & Carcinogenesis
  • Mice, Inbred C57BL
  • Mice
  • Melanoma, Experimental
  • Interleukin-2 Receptor alpha Subunit
  • Immunotherapy, Adoptive