COMBINATION GENE-THERAPY FOR ORAL-CANCER IN A MURINE MODEL

Combination therapy involving adenovirus-mediated transfer of the gene s for herpes thymidine kinase (tk) and murine interleukin 2 (mIL-2) wa s used to treat head and neck cancer in C3H/HeJ mice, Tumors were gene rated by transcutaneous injection of 5 x 10(5) murine squamous carcino ma cells into the floor of the mouth of these syngeneic mice. After 1 week, recombinant adenoviral vectors containing both therapeutic and c ontrol genes in various combinations were injected directly into the e stablished tumors, and subsequently all mice were administered gancicl ovir twice daily (25 mg/kg) for 6 days, Animals receiving either tk al one or tk + mIL-2 demonstrated significant tumor regression compared t o mIL-2 alone or control vector-treated mice (P < 0.008), Mice receivi ng both tk + mIL-2, however, also demonstrated a significantly greater regression of tumors compared to those treated with tk alone (P < 0.0 08), indicating a synergistic effect of the combination gene therapy, This synergism was confirmed in survival studies because Ik + mIL-2-tr eated mice showed increased survivals (P = 0.0002). Clinical and micro scopic exam of regional surrounding tissues and distant organs showed no evidence of cytotoxicity for representative animals in each experim ental 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.