Peptide inhibitors of transforming growth factor-beta enhance the efficacy of antitumor immunotherapy
Palabras clave : 
Regulatory T cells
TGF-β
Inhibitor peptides
Tumor immunotherapy
Fecha de publicación: 
2009
Editorial : 
Wiley blackwell
ISSN: 
0020-7136
Cita: 
Llopiz D, Dotor J, Casares N, Bezunartea J, Diaz-Valdes N, Ruiz M, et al. Peptide inhibitors of transforming growth factor-beta enhance the efficacy of antitumor immunotherapy. Int J Cancer 2009 Dec 1;125(11):2614-2623.
Resumen
Transforming growth factor-beta (TGF-beta) is a cytokine with potent immunosuppressive effects and is overexpressed in many tumors. Therefore, development of molecules able to inhibit TGF-beta is of paramount importance to improve the efficacy of antitumor immunotherapy. TGF-beta inhibitor peptides P144 and P17 were combined with the administration of adjuvant molecules poly(I:C) and agonistic anti-CD40 antibodies, and their effect on the growth of E.G7-OVA established tumors and on antitumor immune response was evaluated. Tumor rejection efficacy of a single administration of adjuvants was enhanced from 15 to 70 % when combined with repeated injections of TGF-beta inhibitor peptides. Simultaneous administration of adjuvants and TGF-beta inhibitor peptides was required for maximal therapeutic efficacy. Although tumor cells produced TGF-beta, it was found that the beneficial effect of peptide administration was mainly due to the inhibition of TGF-beta produced by regulatory CD4(+)CD25(+) T cells rather than by tumor cells. The enhanced antitumor effect was accompanied by a higher activity of dendritic cells, natural killer cells and tumor antigen-specific T cells, as well as by a decrease in the number of myeloid-derived suppressor cells. In conclusion, administration of peptide inhibitors of TGF-beta in therapeutic vaccination enhances the efficacy of immunotherapy by increasing antitumor immune responses. These peptide inhibitors may have important applications for current immunotherapeutic strategies.

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