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Antitumor effects of Newcastle Disease Virus in vivo: local versus systemic effects
V Schirrmacher1, A Griesbach, T Ahlert
1German Cancer Research Center, Division of Cellular Immunology, Tumorimmunology Program, D-69120 Heidelberg, Germany. v.schirrmacher@dkfz-heidelberg.de
Abstract:
Newcastle Disease Virus (NDV) has interesting anti-neoplastic and pleiotropic immune stimulatory properties. The virus preferentially replicates in and kills tumor cells and appears to be safe and to varying degrees effective in phase II-clinical studies in the US and in Europe. Here we have compared various lytic and non-lytic strains of NDV with regard to their antitumor effects after local or systemic application. As tumor models we used human metastatic melanoma xenotransplants in nude mice and murine metastatic colon carcinoma (CT26), renal carcinoma (Renca) and lymphoma (ESb) cell lines. Intra or peri-tumoral application of NDV or NDV infected tumor cells showed more pronounced antitumor activity than systemic application even when in the latter case much higher dose ranges were used. In the CT26 colon carcinoma model the non-lytic strain Ulster showed stronger antitumor activity than the lytic strain 73T. In the human MeWo melanoma xentransplant model strong antitumor bystander effects were observed by 20% admixture of melanoma cells pre-infected in vitro with NDV (either strain Ulster or Italien). Virus therapy of pre-established human melanomas by intra-tumoral injection of NDV was effective with the lytic strain Italien but not with the non-lytic strain Ulster. Systemic anti-metastatic effects were never observed with NDV alone in contrast to previous results obtained with NDV modified tumor vaccines.
Insights
Newcastle Disease Virus (NDV) shows potential as an anti-cancer therapy, with local application proving more effective than systemic delivery. Different NDV strains and delivery methods impact antitumor activity in preclinical models.
Area of Science:
- Oncology
- Virology
- Immunology
Background:
- Newcastle Disease Virus (NDV) exhibits anti-neoplastic and immune-stimulating properties.
- NDV preferentially infects and eliminates tumor cells, showing promise in clinical trials.
Purpose of the Study:
- To compare the antitumor effects of various lytic and non-lytic NDV strains.
- To evaluate local versus systemic application of NDV in preclinical cancer models.
Main Methods:
- Utilized human metastatic melanoma xenotransplants and murine colon carcinoma, renal carcinoma, and lymphoma cell lines.
- Administered NDV via intra-tumoral, peri-tumoral, or systemic routes.
- Assessed antitumor activity and bystander effects of different NDV strains (e.g., Ulster, 73T, Italien).
Main Results:
- Local NDV application demonstrated superior antitumor activity compared to systemic application, even at higher doses.
- In the CT26 colon carcinoma model, the non-lytic Ulster strain outperformed the lytic 73T strain.
- Significant bystander effects were observed in human melanoma models with NDV-infected cell admixtures.
- Intra-tumoral injection of the lytic Italien strain was effective against pre-established melanomas, unlike the non-lytic Ulster strain.
Conclusions:
- Local administration of NDV, particularly specific strains, offers a promising strategy for cancer therapy.
- NDV efficacy is strain-dependent and route-dependent, with local delivery showing greater potential.
- Further research into NDV-based cancer therapies, considering strain and delivery method, is warranted.