Treatment of microscopic pulmonary metastases with recombinant autologous tumor vaccine expressing interleukin 6 and Escherichia coli cytosine deaminase suicide genes

Poorly immunogenic tumor cells genetically transduced to simultaneously express the cytokine interleukin 6 (IL-6) and the bacterial metabolic suicide gene cytosine deaminase (205-IL-6-CD) become highly immunogenic. They are rejected by normal mice without 5-fluorocytosine prodrug treatment. Mice with preexisting wild-type pulmonary micrometastases exhibit prolonged survival and an increased rate of cure when treated with live 205-IL6-CD cells as a therapeutic vaccine. Treatment with these autologous tumor cells producing both the cytokine and the bacterial protein was more effective than treatment with exogenous IL-6 and/or irradiated wild-type tumor cells. Irradiation of the 205-IL6-CD cells significantly reduced their therapeutic efficacy. Therapeutic vaccination with 205-IL6-CD was more effective in animals with wild-type 205 tumor than in animals bearing an unrelated syngeneic tumor. Vaccine efficacy was significantly reduced in animals pretreated with high- dose cyclophosphamide. The results indicate that genetically engineered autologous tumor vaccines may be capable of inducing significant antitumor immunity in hosts of preexisting micrometastatic disease.