Intravascular injections of a conditional replicative adenovirus (adl118) prevent metastatic disease in human breast carcinoma xenografts

We describe a study showing that the adenovirus adl118, lacking both E1B pr oteins, very efficiently kills human malignant cells 'in vitro' and 'in viv o'. Since many breast cancer patients do not have metastasis at the time of diagnosis, but finally develop it, we planned to study whether intravascul ar injections of adl118 could prevent metastatic development. We studied th e effects of this mutant adenovirus in an orthotopic model of human breast carcinoma xenografts with the breast MB435-lung 2 cell line, which is highl y metastatic in the lungs. In this study, all primary tumors were excised w hen they reached 50-100 mm(3) volume in the animals. After surgery, 10(10) p.f.u. of adl118 was intravenously injected into a random group of animals, either three times during the first week only, or once every week. At deat h, almost all the control animals showed numerous lung metastases of large size, which were present in only 15-40% of the treated animals, depending o n the size of the primary tumor at the time of excision. Overall survival w as 50-70 days in control mice, and over 120 days in mice injected with adl1 18. Concomitant treatment with adl118 and cisplatin did not enhance the ant itumor effects of adl118. With these results, we conclude that intravenous injection of conditional replicative adenovirus, after excision of the prim ary tumor, induces a clear decrease in the metastatic disease, and could be a new strategy in preventing tumor metastasis of breast carcinomas.