Two in vitro studies have shown that infection of human immune system cells with NDV causes the cells to produce and release the cytokines interferon-alpha and tumor necrosis factor (TNF)-alpha.[6,8] In one of these studies, it was shown further that infection of human cancer cells with NDV makes the cells more sensitive to the cytotoxic effects of TNF-alpha.
Additional in vitro studies have shown that NDV-infected human cancer cells are better at activating human cytotoxic T cells, helper T cells, and natural killer cells than uninfected cancer cells.[8,29,30,48] The NDV protein hemagglutinin-neuraminidase, which is present in the plasma membrane of virus-infected cells, appears to play a role in the enhancement of T cell activation. There is evidence that this protein makes infected cells more adhesive, thereby promoting the interaction between virus-infected cells and immune system cells. Reviewed in 
Other laboratory studies have shown that the interaction between NDV-infected cancer cells and T cells can be improved if monoclonal antibodies that bind the hemagglutinin-neuraminidase protein on the cancer cells and either the CD3 protein or the CD28 protein on T cells (i.e., bispecific monoclonal antibodies) are also used.[29,38,49,50] Reviewed in [20,44,47] It has been reported that this improved interaction leads to better T cell activation.[29,38] Reviewed in [20,44,47] T cells exposed to NDV-infected human colon cancer cells and bispecific monoclonal antibodies showed not only an increased ability to kill the virus-infected cells but also an ability to inhibit the proliferation of uninfected colon cancer cells.[29,38] Reviewed in  On the basis of these and other in vitro findings, it has been proposed that vaccines consisting of NDV-infected cancer cells and bispecific monoclonal antibodies be tested in humans.[20,29,38,44,47]
As noted above, animal cells and animal tumor models have also been used to explore the immunotherapy potential of NDV. ESb, a mouse model of metastatic T-cell lymphoma has been employed in most of this work;[25,28,31,35,36,37,39,40] Reviewed in [11,20,43,44,45,46,47] however, additional experiments have utilized one or more of the following tumor models: mouse B16 melanoma, mouse Lewis lung carcinoma,[32,35] mouse P815 mastocytoma, mouse Ca 761-P93 mammary carcinoma, and guinea pig L10 hepatocellular carcinoma.
In one study, it was shown that anticancer activity could be induced in mouse macrophages both in vitro and in vivo by infection with NDV strain Ulster. Similar activation of mouse macrophages in vitro was observed after infection with the NDV lytic strain Lasota. In this study, the activated macrophages showed cytotoxic activity toward ESb, P815 mastocytoma, and Ca 761-P93 mammary carcinoma cells in vitro. Other experiments demonstrated that much of the observed anticancer activity could be attributed to the production and release of TNF-alpha by the infected macrophages. In addition, the infected, activated macrophages showed anticancer activity in vivo when they were injected into mice bearing Ca 761-P93 mammary carcinoma or Lewis lung carcinoma tumors. Human macrophages stimulated with NDV Ulster have also been shown to kill various types of human tumor cells.