Alpha(v)beta(3) integrin-mediated adenoviral transfer of interleukin-12 at the periphery of hepatic colon cancer metastases induces VCAM-1 expression and T-cell recruitment
Palabras clave : 
Gene therapy
avb3 (CD51/CD61)
Adenovirus
VCAM-1 (CD106)
Interleukin-12
Adoptive T-cell therapy;
Immunotherapy
Colon cancer
Fecha incorporación: 
2001
Editorial : 
Nature Publishing Group
ISSN: 
1525-0024
Cita: 
Mazzolini G, Narvaiza I, Bustos M, Duarte M, Tirapu I, Bilbao R, et al. Alpha(v)beta(3) integrin-mediated adenoviral transfer of interleukin-12 at the periphery of hepatic colon cancer metastases induces VCAM-1 expression and T-cell recruitment. Mol Ther 2001 May;3(5 Pt 1):665-672.
Resumen
We previously reported that systemic injection of recombinant adenovirus resulted in a rim of gene transduction around experimental liver tumor nodules. This zone of higher infection is dependent on the alpha(v)beta(3) integrin, acting as an adenovirus internalization receptor, which is overexpressed in tissues surrounding liver metastases. When a recombinant adenovirus encoding interleukin-12 (AdCMVIL-12) is given into a subcutaneous tumor nodule in mice also bearing concomitant liver tumors, a fraction of AdCMVIL-12 reaches the systemic circulation and infects liver tissue, especially at the malignant/healthy tissue interface. As a result of the expression at this location of the interleukin-12 transgenes, VCAM-1 is induced on vessel cells and mediates the recruitment of adoptively transferred anti-tumor cytolytic T-lymphocytes. These studies provide mechanistic explanations for the potent therapeutic synergy observed between interleukin-12 gene transfer and adoptive T-cell therapy.

Ficheros en este registro:
Fichero: 
MolTher20013665.pdf
Descripción: 
Tamaño: 
391,93 kB
Formato: 
Adobe PDF


Los ítems de Dadun están protegidos por copyright, con todos los derechos reservados, a menos que se indique lo contrario.