Systemic tumor targeting and killing by Sindbis viral vectors

• DOI: 10.1038/nbt917
• Publication Date: 2003-11-30T18:05:31Z
• Authors: Jen-Chieh Tseng; Brandi Levin; Alicia Hurtado; Herman Yee; Ignacio Perez de ...; Maria Jimenez; Peter Shamamian; Ruzhong Jin; Richard P Novick; Angel Pellicer; Daniel Meruelo
• Keywords: 0303 health sciences; Time Factors; Genetic Vectors; Genetic Therapy; Mice, SCID; Immunohistochemistry; Cell Line; 3. Good health; Mice, Inbred C57BL; Mice; 03 medical and health sciences; Neoplasms; Animals; Female; Sindbis Virus; Neoplasm Metastasis; Luciferases; Neoplasm Transplantation

Successful cancer gene therapy requires a vector that systemically and specifically targets tumor cells throughout the body. Although several vectors have been developed to express cytotoxic genes via tumor-specific promoters or to selectively replicate in tumor cells, most are taken up and expressed by just a few targeted tumor cells. By contrast, we show here that blood-borne Sindbis viral vectors systemically and specifically infect tumor cells. A single intraperitoneal treatment allows the vectors to target most tumor cells, as demonstrated by immunohistochemistry, without infecting normal cells. Further, Sindbis infection is sufficient to induce complete tumor regression. We demonstrate systemic vector targeting of tumors growing subcutaneously, intrapancreatically, intraperitoneally and in the lungs. The vectors can also target syngeneic and spontaneous tumors in immune-competent mice. We document the anti-tumor specificity of a vector that systemically targets and eradicates tumor cells throughout the body without adverse effects.