Newcastle Disease Virus (NDV), an agent with interesting immune stimulatory and anti-
tumor activity, was investigated for its capacity to activate anti-
tumor activity in murine macrophages in vitro and in vivo. Direct macrophage activation was seen under a variety of experimental conditions using two different strains of NDV, different sources of macrophages (spleen and peritoneum) and different strains of mice (DBA/2, C57BL/6, 615). Various macrophage
enzymes (ADA, iNOS,
lysozyme,
acid phosphatase) became upregulated and anti-
tumor effector molecules such as
nitric oxide (NO) and
TNF-alpha were found in the supernatant. NDV activated macrophages performed anti-
tumor activity in vitro such as anti-
tumor cytostasis and anti-
tumor cytotoxicity. The cytotoxic anti-
tumor activity was broad and active against all
tumor 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 mixed lymphocyte culture
conditioned medium had restricted anti-
tumor activity. Anti-
tumor activity of NDV activated macrophages could be transfered in vivo. Transfer of macrophages which had not been appropriately activated exerted either no effect or a
tumor growth augmenting effect. Repeated intravenous transfer of NDV activated macrophages exerted a significant suppressive effect on pulmonary
metastases in a mammary
carcinoma tumor model as well as in a lung
carcinoma model. Taken together these results demonstrate that NDV can strongly activate macrophages to perform anti-
tumor activities in vitro and in vivo.