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Dadun > Depósito Académico > CIMA (Centro de Investigación Médica Aplicada) > Área de Terapia génica y Hepatología > Inmunología hepatitis virales > DA - CIMA - Terapia génica y Hepatología - Inmunología hepatitis virales - Artículos de revista >

Peptide inhibitors of transforming growth factor-beta enhance the efficacy of antitumor immunotherapy
Authors: Llopiz, D. (Diana)
Dotor, J. (Javier)
Casares, N. (Noelia)
Bezunartea, J. (Jaione)
Diaz-Valdes, N. (Nancy)
Ruiz, M. (Marta)
Aranda, F. (Fernando)
Berraondo, P. (Pedro)
Prieto, J. (Jesús)
Lasarte, J.J. (Juan José)
Borras-Cuesta, F. (Francisco)
Sarobe, P. (Pablo)
Keywords: Regulatory T cells
TGF-β
Inhibitor peptides
Tumor immunotherapy
Issue Date: 2009
Publisher: Wiley blackwell
Publisher version: http://dx.doi.org/ 10.1002/ijc.24656
ISSN: 0020-7136
Citation: 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.
Abstract
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.
Permanent link: http://hdl.handle.net/10171/20419
Appears in Collections:DA - CIMA - Terapia génica y Hepatología - Terapia génica del cáncer - Artículos de revista
DA - Medicina - Medicina Interna - Artículos de revista
DA - CIMA - Terapia génica y Hepatología - Inmunología experimental - Artículos de revista
DA - CIMA - Terapia génica y Hepatología - Inmunología hepatitis virales - Artículos de revista

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