The ability of lytic strains of NDV to kill human cancer cells in vivo has also been examined. In xenograft studies, human cancer cells were injected either subcutaneously or intradermally into athymic, nude mice (i.e., mice that do not reject tumor cells from other animals because they have a defective immune system), and tumors were allowed to form. NDV was injected directly into the tumors, and tumor growth and animal survival were monitored.
Intratumoral injection of strain 73-T was associated with complete tumor regression in 75% to 100% of mice bearing human fibrosarcoma, neuroblastoma, or cervical carcinoma tumors.[1,2,3,10] Intratumoral injection of 73-T was also associated with more than 80% tumor regression in 66% of mice bearing human synovial sarcoma tumors. In addition, intratumoral injection of 73-T was associated with 68% to 96% inhibition of tumor growth in mice bearing human epidermoid, colon, lung, breast, or prostate carcinoma tumors.
Intratumoral injection of strain Italien was associated with complete tumor regression in 100% of mice bearing human melanoma tumors. The growth of metastatic tumors in these animals, however, was not affected, suggesting that the virus was unable to disseminate widely throughout the body. Reviewed in [14,20]
Replication of strain 73-T in the above-mentioned neuroblastoma xenografts was demonstrated by showing an increase in the amount of virus that could be recovered from tumor samples over time. When this strain was injected into the thigh muscle of athymic, nude mice, the amount of virus that could be recovered decreased with time, a finding consistent with the proposal that NDV replicates much more efficiently in cancer cells than in most normal cells.
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]