Systemic tumor targeting and killing by Sindbis viral vectors

• Published in: Nature biotechnology Vol. 22; no. 1; pp. 70 - 77
• Main Authors: Meruelo, Daniel, Tseng, Jen-Chieh, Levin, Brandi, Hurtado, Alicia, Yee, Herman, de Castro, Ignacio Perez, Jimenez, Maria, Shamamian, Peter, Jin, Ruzhong, Novick, Richard P, Pellicer, Angel
• Format: Journal Article
• Language: English
• Published: New York, NY Nature 01.01.2004; Nature Publishing Group
• Subjects: Animals; Biological and medical sciences; Bioluminescence; Biotechnology; Blood; Cancer therapies; Cell death; Cell Line; Confidence intervals; Cytotoxicity; Female; Fundamental and applied biological sciences. Psychology; Gene therapy; Genetic Therapy - methods; Genetic Vectors; Health. Pharmaceutical industry; Immunohistochemistry; Industrial applications and implications. Economical aspects; Infections; Luciferases - metabolism; Mice; Mice, Inbred C57BL; Mice, SCID; Neoplasm Metastasis; Neoplasm Transplantation; Neoplasms - therapy; Side effects; Sindbis virus; Sindbis Virus - genetics; Time Factors; Tumors; Vectors (Biology); New York; United States > US; Virus; Vertebrata; Mammalia; Targeting; Mouse; Rodentia; Togaviridae; Alphavirus; Tumor; Gene therapy; Vector; Sindbis virus
• DOI: 10.1038/nbt917
• ISSN: 1087-0156

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.