Combination gene therapy for oral cancer in a murine model

Combination therapy involving adenovirus-mediated transfer of the genes for herpes thymidine kinase (tk) and murine interleukin 2 (mIL-2) was used to treat head and neck cancer in C3H/HeJ mice. Tumors were generated by transcutaneous injection of 5 x 10⁵ murine squamous carcinoma cells into the floor of the mouth of these syngeneic mice. After 1 week, recombinant adenoviral vectors containing both therapeutic and control genes in various combinations were injected directly into the established tumors, and subsequently all mice were administered ganciclovir twice daily (25 mg/kg) for 6 days. Animals receiving either tk alone or tk + mIL-2 demonstrated significant tumor regression compared to mIL-2 alone or control vector- treated mice (P < 0.008). Mice receiving both tk + mIL-2, however, also demonstrated a significantly greater regression of tumors compared to those treated with tk alone (P < 0.008), indicating a synergistic effect of the combination gene therapy. This synergism was confirmed in survival studies because tk + mIL-2-treated mice showed increased survivals (P = 0.0002). Clinical and microscopic exam of regional surrounding tissues and distant organs showed no evidence of cytotoxicity for representative animals in each experimental group. These results suggest that combination tk and mIL-2 gene therapy may provide a powerful new modality for the treatment of head and neck cancer.