Another study of intratumoral injection used the V4UPM strain of NDV in a nude mouse model of tumors produced by subcutaneous injection of human glioblastoma multiform cells. All four mice with tumors from the U-87MG cell line experienced sustained complete responses after one injection. However, no complete responses were observed in mice with tumors from the DBTRG.05MG cell line despite a similar in vitro cytotoxicity compared with U-87MG.
In one study, mice bearing human neuroblastoma xenografts were given single intraperitoneal injections of strain 73-T, and 9 (75%) of 12 treated mice exhibited complete, durable tumor regressions.
It is important to note that athymic, nude mice still make small numbers of T cells, and they produce interferons, natural killer cells, and macrophages. Reviewed in [11,26,27] The possibility that these residual components of the immune system, which may be activated by the presence of NDV, contributed to the antitumor effects observed in the xenograft studies cannot be ruled out.
NDV and Cancer Immunotherapy
Other laboratory and animal studies have shown that NDV and NDV-infected cancer cells can stimulate a variety of immune system responses that are essential to the successful immunotherapy of cancer.[6,8,25,28,29,30,31,32,33,34,35,36,37,38,39,40,41,42] Reviewed in [11,20,43,44,45,46,47] A few of these studies used human cells,[6,8,29,30,38,41,42] Reviewed in [20,44,47] but most used animal cells and animal tumor models.[6,8,25,28,30,31,32,33,34,35,36,37,39] Reviewed in [11,20,43,44,45,46]
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