Recombinant adenoviral vectors have adjuvant activity and stimulate T cellresponses against tumor cells

The host-immune response against adenoviruses forms a major obstacle for th eir use as gene therapy vectors for treatment of genetic defects. None the less, they are the preferred vectors for in vivo gene transfer in experimen tal gene therapy protocols for cancer. In this article we demonstrate the a ntitumor efficacy of adenovirus-mediated transfer of human interleukin-2 cD NA in the rat-CC531 model for hepatic metastases of colorectal cancer intra tumoral administration of 10(8) plaque-forming units of the hIL-2-expressin g adenoviral vector, AdCAIL-2, resulted in a cessation of tumor growth in 8 0% of the injected tumors. In control groups receiving AdCnull, a vector wi th the same viral backbone, but lacking transgene expression, none of the t umors responded. However, intratumoral treatment with this vector significa ntly enhanced tumor regression induced by systemic IL-2 protein treatment, which was used as a positive control. In addition we show, by performing de layed-type of hypersensitivity assays, that AdCnull when injected intratumo rally enhances recognition of tumor antigens by T lymphocytes to the same e xtent as intratumoral treatment with the IL-2-expressing vector. The replic ation-deficient adenoviruses appear to have a therapeutic advantage in cyto kine-mediated immunotherapy: even adenovirus vectors that do not express a transgene, show adjuvant activity and stimulate an antitumor immune respons e.