Journal
JOURNAL OF IMMUNOLOGY
Volume 185, Issue 9, Pages 5150-5159Publisher
AMER ASSOC IMMUNOLOGISTS
DOI: 10.4049/jimmunol.1001114
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Funding
- Fundacion Mutua Madrilena, Ministerio de Educacion y Ciencia [SAF2007-61432, SAF2010-15060]
- UTE
- Ministerio de Ciencia e Innovacion
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Immunosuppressive activity of regulatory T cells (Treg) may contribute to the progression of cancer or infectious diseases by preventing the induction of specific immune responses. Using a phage-displayed random peptide library, we identified a 15-mer synthetic peptide, P60, able to bind to forkhead/winged helix transcription factor 3 (FOXP3), a factor required for development and function of Treg. P60 enters the cells, inhibits FOXP3 nuclear translocation, and reduces its ability to suppress the transcription factors NF-kappa B and NFAT. In vitro, P60 inhibited murine and human-derived Treg and improved effector T cell stimulation. P60 administration to newborn mice induced a lymphoproliferative autoimmune syndrome resembling the reported pathology in scurfy mice lacking functional Foxp3. However, P60 did not cause toxic effects in adult mice and, when given to BALB/c mice immunized with the cytotoxic T cell epitope AH1 from CT26 tumor cells, it induced protection against tumor implantation. Similarly, P60 improved the antiviral efficacy of a recombinant adenovirus expressing NS3 protein from hepatitis C virus. Functional inhibition of Treg by the FOXP3-inhibitory peptide P60 constitutes a strategy to enhance antitumor and antiviral immunotherapies. The Journal of Immunology, 2010, 185: 5150-5159.
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