Antitumor effects of Newcastle disease virus in vivo: local versus systemic effects

Newcastle Disease Virus (NDV) has interesting anti-neoplastic and pleiotrop ic immune stimulatory properties. The virus preferentially replicates in an d kills tumor cells and appears to be safe and to varying degrees effective in phase II-clinical studies in the US and in Europe. Here we have compare d various lytic and non-lytic strains of NDV with regard to their antitumor effects after local or systemic application. As tumor models we used human metastatic melanoma xenotransplants in nude mice and murine metastatic col on carcinoma (CT26), renal carcinoma (RENCA) and lymphoma (ESb) cell lines. Intra or peri-tumoral application of NDV or NDV infected tumor cells showe d more pronounced antitumor activity than systemic application even when in the latter case much higher dose ranges were used. In the CT26 colon carci noma model the non-lytic strain Ulster showed stronger antitumor activity t han the lytic strain 73T. In the human MeWo melanoma xentransplant model st rong antitumor bystander effects were observed by 20% admixture of melanoma cells pre-infected in vitro with NDV (either strain Ulster or Italien). Vi rus therapy of pre-established human melanomas by intra-tumoral injection o f NDV was effective with the lytic strain Italien but not with the non-lyti c strain Ulster. Systemic anti-metastatic effects were never observed with NDV alone in contrast to previous results obtained with NDV modified tumor vaccines.