Systemic tumor targeting and killing by Sindbis viral vectors
This sounds almost too good to be true (granted, we're talking about mice). Is it ?
Published online: 30 November 2003, doi:10.1038/nbt917
January 2004 Volume 22 Number 1 pp 70 - 77
Jen-Chieh Tseng1, Brandi Levin1, Alicia Hurtado1, Herman Yee1, Ignacio Perez de Castro1, Maria Jimenez1, Peter Shamamian2, Ruzhong Jin3, Richard P Novick3, Angel Pellicer1 & Daniel Meruelo1
1. New York University (NYU) Gene Therapy Center, NYU Cancer Institute and Department of Pathology, NYU School of Medicine, 550 First Avenue, New York, New York 10016, USA.
2. Department of Surgery, NYU School of Medicine, 550 First Avenue, New York, New York 10016, USA.
3. Molecular Pathogenesis Program, Skirball Institute, Department of Microbiology and Department of Medicine, NYU School of Medicine, 550 First Avenue, New York, New York 10016, USA.
Correspondence should be addressed to D Meruelo. e-mail: daniel.meruelo@med.nyu.edu
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 seclectively 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. |
