Newcastle Disease Virus activates macrophages for anti-tumor activity

Newcastle Disease Virus (NDV), an agent with interesting immune stimulatory and anti-tumor activity, was investigated for its capacity to activate ant i-tumor activity in. murine macrophages in vitro and in vivo. Direct macrop hage activation was seen under a variety of experimental conditions using t wo different strains of NDV, different sources of macrophages (spleen and p eritoneum) and different strains of mice (DBA/2, C57BL/6, 615). Various mac rophage enzymes (ADA, iNOS, lysozyme, acid phosphatase) became upregulated and anti-tumor effector molecules such as nitric oxide (NO) and TNF-alpha w ere found in the supernatant. NDV activated macrophages performed anti-tumo r activity in vitro such as anti-tumor cytostasis and anti-tumor cytotoxici ty. The cytotoxic anti-tumor activity was broad and active against all tumo r lines tested including mammary carcinoma, lung carcinoma, mastocytoma and immune escape variants (lymphoma). Macrophage activation via BCG/LPS also caused a broad range anti-tumor cytotoxic activity while activation via mix ed lymphocyte culture conditioned medium had restricted anti-tumor activity . Anti-tumor activity of NDV activated macrophages could be transfered in v ivo. Transfer of macrophages which had not been appropriately activated exe rted either no effect or a tumor growth augmenting effect. Repeated intrave nous transfer of NDV activated macrophages exerted a significant suppressiv e effect on pulmonary metastases in a mammary carcinoma tumor model as well as in a lung carcinoma model. Taken together these results demonstrate tha t NDV can strongly activate macrophages to perform anti-tumor activities in vitro and in vivo.