Vaccination against the forkhead family transcription factor Foxp3 enhances tumor immunity

Smita Nair, David Boczkowski, Martin Fassnacht, David Pisetsky, Eli Gilboa

Research output: Contribution to journalArticle

120 Citations (Scopus)

Abstract

Depletion of CD4+CD25+ regulatory T cells (Treg) by treatment with αCD25 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 αCD25 antibody administration. In contrast to αCD25 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 αCD25 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.

Original languageEnglish
Pages (from-to)371-380
Number of pages10
JournalCancer Research
Volume67
Issue number1
DOIs
StatePublished - Jan 1 2007

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Forkhead Transcription Factors
Immunity
Vaccination
Antibodies
Neoplasms
Vaccines
Interleukin-2 Receptors
Autoantigens
Regulatory T-Lymphocytes
Autoimmunity
Dendritic Cells
Thymus Gland
Therapeutics
T-Lymphocytes
Messenger RNA

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Vaccination against the forkhead family transcription factor Foxp3 enhances tumor immunity. / Nair, Smita; Boczkowski, David; Fassnacht, Martin; Pisetsky, David; Gilboa, Eli.

In: Cancer Research, Vol. 67, No. 1, 01.01.2007, p. 371-380.

Research output: Contribution to journalArticle

Nair, Smita ; Boczkowski, David ; Fassnacht, Martin ; Pisetsky, David ; Gilboa, Eli. / Vaccination against the forkhead family transcription factor Foxp3 enhances tumor immunity. In: Cancer Research. 2007 ; Vol. 67, No. 1. pp. 371-380.
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