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 (AdCMVmIL2) 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 (≤mm³), intratumor injection of AdCMVmIL2 led to mMTC tumor regression in up to 69% of animals. With large tumors (>30 mm³), almost all treated tumors showed stabilization in size, but did not completely resolve. All mice cured by AdCMVmIL2 treatment failed to develop tumors after reinjection of wild-type mMTC cells, indicating that long-term antitumor immunity developed. Analysis of cytotoxicity indicates that the antitumor effect in cured mice was dependent on cytotoxic T lymphocyte (CTL) activity against the tumor. Histological and immunohistological studies of treated tumors revealed massive CD4⁺ and CD8⁺ cell infiltration in AdCMVmIL2 treated tumors, but not in untreated or control virus treated tumors. The data demonstrate the ability of interleukin 2 (IL-2) to elicit specific antitumor immunity and offer hope for this therapy in humans.