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Published on: April 15, 2016
Host mediated anti-tumor effect of oncolytic Newcastle disease virus after locoregional application
Leonidas Apostolidis1, Volker Schirrmacher, Philippe Fournier
1Division of Cellular Immunology, German Cancer Research Center, Im Neuenheimer Feld 18-20, D-69120 Heidelberg, Germany.
Abstract:
Several strains of the Newcastle disease virus (NDV) have raised considerable interest in recent years for clinical application because of their oncolytic properties. In this study we characterized virological, immunological and anti-tumor properties of some NDV strains. The oncolytic strain MTH-68/H was the most potent interferon-alpha inducer and, after UV light inactivation, it was the only tested NDV strain which induced in human PBMC anti-tumor activity in vitro. Upon systemic application to mice bearing a virus susceptible intradermal tumor, no significant anti-tumor effects were observed with the two oncolytic strains Italian and MTH-68/H while the treatment had significant side effects as seen by loss of body weight. In contrast, when using a locoregional application model for treatment of liver metastases of luciferase transfected CT26 colon carcinoma cells, MTH-68/H showed a significant delay in tumor growth, as well as prolonged survival but no effects on body weight. Surprisingly, this CT26 murine tumor cell transfectant was resistant in vitro to virus infection and oncolysis. These results suggest: i) that locoregional application of oncolytic NDV is more effective than systemic i.v. application; and ii) that oncolytic NDV can mediate effects even against a virus-resistant tumor line. The involvement of host anti-tumor immune responses as an important mechanism in therapies based on oncolytic NDV will be discussed.
Insights
Newcastle disease virus (NDV) shows oncolytic potential. Locoregional application of MTH-68/H strain demonstrated significant anti-tumor effects against liver metastases, even in virus-resistant tumors, suggesting a promising therapeutic strategy.
Area of Science:
- Virology and Immunology
- Oncolytic Virus Therapy
- Cancer Research
Background:
- Newcastle disease virus (NDV) strains exhibit oncolytic properties, making them candidates for cancer therapy.
- The MTH-68/H strain is a potent inducer of interferon-alpha and demonstrates in vitro anti-tumor activity.
- Previous studies showed limited efficacy and side effects with systemic application of oncolytic NDV.
Purpose of the Study:
- To characterize the virological, immunological, and anti-tumor properties of specific NDV strains.
- To evaluate the efficacy of systemic versus locoregional application of oncolytic NDV in preclinical tumor models.
- To investigate the potential of NDV to overcome tumor resistance to viral infection.
Main Methods:
- Characterization of NDV strains for interferon-alpha induction and in vitro anti-tumor activity using human peripheral blood mononuclear cells (PBMCs).
- Assessment of systemic anti-tumor effects and side effects (body weight loss) of Italian and MTH-68/H NDV strains in mice with intradermal tumors.
- Evaluation of locoregional application of MTH-68/H NDV in a mouse model of liver metastases from CT26 colon carcinoma cells.
Main Results:
- The MTH-68/H NDV strain was the most potent interferon-alpha inducer and showed in vitro anti-tumor activity after UV inactivation.
- Systemic application of Italian and MTH-68/H NDV strains resulted in no significant anti-tumor effects and caused body weight loss in mice.
- Locoregional application of MTH-68/H NDV significantly delayed tumor growth and prolonged survival in mice with liver metastases, despite the tumor cells being resistant to oncolysis in vitro.
Conclusions:
- Locoregional application of oncolytic NDV is more effective than systemic administration for treating certain tumors.
- Oncolytic NDV can exert therapeutic effects against virus-resistant tumors, potentially through host-mediated immune responses.
- Further investigation into the immunological mechanisms underlying oncolytic NDV therapy is warranted.
