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

Eradication of large tumors expressing human papillomavirus E7 protein by therapeutic vaccination with E7 fused to the extra domain a from fibronectin
Authors: Mansilla, C. (Cristina)
Berraondo, P. (Pedro)
Durantez, M. (Maika)
Martinez, M. (Marta)
Casares, N. (Noelia)
Arribillaga, L. (Laura)
Rudilla, F. (Francesc)
Fioravanti, J. (Jessica)
Lozano, T. (Teresa)
Villanueva, L. (Lorea)
Sarobe, P. (Pablo)
Borras-Cuesta, F. (Francisco)
Leclerc, C. (Claude)
Prieto, J. (Jesús)
Lasarte, J.J. (Juan José)
Keywords: Cervical carcinoma
Dendritic cell
Therapeutic vaccine
TLR4
EDA
Issue Date: 2011
Publisher: Wiley-Blackwell
Publisher version: http://onlinelibrary.wiley.com/doi/10.1002/ijc.26412/abstract
ISSN: 1097-0215
Citation: Mansilla C, Berraondo P, Durantez M, Martinez M, Casares N, Arribillaga L, et al. Eradication of large tumors expressing human papillomavirus E7 protein by therapeutic vaccination with E7 fused to the extra domain a from fibronectin. Int J Cancer 2011 Sep 2.
Abstract
Cervical carcinoma is one of the most common cancers in women worldwide. It is well established that chronic infection of the genital tract by various mucosatropic human papillomavirus (HPV) types causes cervical cancer. Cellular immunity to E7 protein from HPV (HPVE7) has been associated with clinical and cytologic resolution of HPV-induced lesions. Thus, we decided to test if targeting of HPVE7 to dendritic cells using a fusion protein containing the extra domain A (EDA) from fibronectin, a natural ligand for TLR4, and HPVE7 (EDA-HPVE7) might be an efficient vaccine for the treatment of cervical carcinoma. We found that EDA-HPVE7 fusion protein was efficiently captured by bone marrow derived dendritic cells in vitro and induced their maturation, with the upregulation of maturation markers and the production of IL-12. Immunization of mice with EDA-HPVE7 fusion protein induced antitumor CD8(+) T cell responses in the absence of additional adjuvants. Repeated intratumoral administration of EDA-HPVE7 in saline was able to cure established TC-1 tumors of 5-7 mm in diameter. More importantly, intravenous injection with EDA-HPVE7 in combination with the TLR ligand polyinosinic-polycytidylic acid (pIC), or with low doses of cyclophosphamide and the TLR9 ligand CpG-B complexed in cationic lipids, were able to eradicate large established TC-1 tumors (1.2 cm in diameter). Thus, therapeutic vaccination with EDA-HPVE7 fusion protein may be effective in the treatment of human cervical carcinoma
Permanent link: http://hdl.handle.net/10171/21651
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 hepatitis virales - Artículos de revista
DA - CIMA - Terapia génica y Hepatología - Inmunología experimental - Artículos de revista

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