In vivo surgical resection plus adjuvant gene therapy in the treatment of mammary and prostate cancer

Adenoviral-mediated gene therapy delivery, combining the herpes simplex vir us thymidine kinase gene (Ad-tk) with gancyclovir, has been evaluated as a treatment modality for numerous tumors in the laboratory and in the clinics . As a single modality, gene therapy has shown some promising local and sys temic results but no curative success. Surgery is the standard of care for many solid tumors. However, minor residual tumor following surgical resecti on can lead to local recurrence, and surgery is neither efficient nor plaus ible for metastatic disease. In this study, two tumor models were used to e valuate the effects of Ad-tk gene therapy as an adjuvant to surgery. Subcut aneous mammary- and prostate-derived tumors were produced in syngeneic mice . To evaluate systemic effects, tumor cells were injected intravenously, wi th subsequent formation of lung nodules. The subcutaneous tumors were surgi cally resected and the tumor bed was bathed with saline or Ad-tk. The anima ls were evaluated for toxicity, local tumor recurrence, survival, and lung nodule formation. No evidence of additional toxicity was observed. In the l ess aggressive mammary model, the time to recurrence was increased from 11. 7 (+/-1.0) days to 22.7 (+/-5.5) days. In the prostate model, recurrence we nt from a mean of 17.3 (+/-5.6) to 22.6 (+/-6.8) days. Survival was also im proved from a mean of 19.7 (+/-1.1) to 32.3 (+/-4.8) and 26.1 (+/-5.0) to 3 4.1 (+/-6.1) days in the mammary and prostate models, respectively. Evidenc e of systemic benefits from the use of adjuvant Ad-tk therapy was demonstra ted by a significant reduction in lung nodules from a mean of 17 to 3.5. Th ese results suggest that Ad-tk gene therapy may be a useful adjuvant for pa tients undergoing surgery for treatment of cancer.