Nonlytic NDV strain Ulster has also been shown to replicate efficiently in human cancer cells in vitro, including cells of the following types of human tumors:
- Colorectal carcinoma.
- Gastric carcinoma.
- Pancreatic carcinoma.
- Ovarian carcinoma.
Renal cell carcinoma.
- Lung carcinoma.
- Larynx carcinoma.
- Cervical carcinoma.
- B-cell lymphoma.
- T-cell lymphoma.
This strain does not replicate efficiently in normal human white blood cells in vitro. Other experiments have shown that NDV Ulster can kill infected cells [14,26] and that it can replicate in human cancer cells regardless of cell cycle.[7,21]
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. Injection produced 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 inhibited 68% to 96% 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 was not affected, suggesting that the virus was unable to disseminate widely throughout the body.[11,14,21]
In the above-mentioned neuroblastoma xenograft study, strain 73-T replicated over time in tumor tissue but replicated poorly when injected into the thigh muscle of athymic, nude mice. This finding is consistent with the proposal that NDV replicates more efficiently in cancer cells than in most normal cells.
In another nude mouse study, strain V4UPM inhibited the growth of some cell lines of subcutaneously injected human glioblastoma multiforme 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.