alpha(v)beta(3) integrin-mediated adenoviral transfer of interleukin-12 atthe periphery of hepatic colon cancer metastases induces VCAM-1 expressionand T-cell recruitment

We previously reported that systemic injection of recombinant adenovirus re sulted in a rim of gene transduction around experimental liver tumor nodule s. This zone of higher infection is dependent on the cu,P, integrin, acting as an adenovirus internalization receptor, which is overexpressed in tissu es surrounding liver metastases. When a recombinant adenovirus encoding int erleukin-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 o f the interleukin-12 transgenes, VCAM-1 is induced on vessel cells and medi ates the recruitment of adoptively transferred anti-tumor cytolytic T-lymph ocytes. These studies provide mechanistic explanations for the potent thera peutic synergy observed between interleukin-12 gene transfer and adoptive T -cell therapy.