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Systemic tumor targeting and killing by Sindbis viral vectors
Jen-Chieh Tseng1, Brandi Levin, Alicia Hurtado
1New York University Gene Therapy Center, NYU Cancer Institute, NYU School of Medicine, 550 First Avenue, New York, New York 10016, USA.
Nature Biotechnology
|December 3, 2003
Summary
Blood-borne Sindbis viral vectors effectively target and infect most cancer cells throughout the body. This systemic cancer gene therapy approach leads to complete tumor regression without harming healthy cells.
Area of Science:
- Oncology
- Virology
- Gene Therapy
Background:
- Effective cancer gene therapy necessitates systemic and specific tumor cell targeting.
- Current vectors often exhibit limited uptake and expression in targeted tumor cells.
Purpose of the Study:
- To evaluate the systemic and specific tumor-targeting capabilities of blood-borne Sindbis viral vectors.
- To assess the efficacy of Sindbis viral vectors in inducing tumor regression.
Main Methods:
- Administration of Sindbis viral vectors via intraperitoneal injection.
- Immunohistochemical analysis to assess vector targeting and infection in tumor cells.
- Evaluation of tumor regression in various tumor models, including subcutaneous, intrapancreatic, intraperitoneal, and lung tumors.
Main Results:
- Sindbis viral vectors demonstrated systemic and specific infection of tumor cells across diverse tumor locations.
- A single treatment resulted in targeting of the majority of tumor cells without infecting normal cells.
- Complete tumor regression was achieved following Sindbis infection.
- Vectors successfully targeted syngeneic and spontaneous tumors in immune-competent mice.
Conclusions:
- Blood-borne Sindbis viral vectors offer a promising strategy for systemic cancer gene therapy.
- These vectors exhibit high specificity for tumor cells, leading to effective eradication and complete tumor regression with no observed adverse effects.