Genetic immunotherapy for medullary thyroid carcinoma: Destruction of tumors in mice by in vivo delivery of adenoviral vector transducing the murine interleukin-2 gene

A replication defective adenovirus harboring the interleukin-2 gene (AdCMVm IL2) was used for treatment of a mouse medullary thyroid carcinoma (mMTC). We evaluated the antitumor effect and immunological response in the animal model. In small tumors (less than or equal to 30 mm(3)), intratumor injecti on of AdCMVmIL2 led to mMTC tumor regression in up to 69% of animals. With large tumors (>30 mm(3)), almost all treated tumors showed stabilization in size, but did not completely resolve. All mice cured by AdCMVmIL2 treatmen t failed to develop tumors after reinjection of wild-type mMTC cells, indic ating that long-term antitumor immunity developed. Analysis of cytotoxicity indicates that the antitumor effect in cured mice was dependent on cytotox ic T lymphocyte (CTL) activity against the tumor. Histological and immunohi stological studies of treated tumors revealed massive CD4(+) and CD8(+) cel l infiltration in AdCMVmIL2 treated tumors, but not in untreated or control virus treated tumors. The data demonstrate the ability of interleukin 2 (I L-2) to elicit specific antitumor immunity and offer hope for this therapy in humans.