Systemic tumor targeting and killing by Sindbis viral vectors

Jen Chieh Tseng, Brandi Levin, Alicia Hurtado, Herman Yee, Ignacio Perez De Castro, Maria Jimenez, Peter Shamamian, Ruzhong Jin, Richard P. Novick, Angel Pellicer, Daniel Meruelo

Research output: Contribution to journalArticle

126 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)70-77
Number of pages8
JournalNature biotechnology
Volume22
Issue number1
DOIs
StatePublished - Jan 1 2004
Externally publishedYes

ASJC Scopus subject areas

  • Biotechnology
  • Bioengineering
  • Applied Microbiology and Biotechnology
  • Molecular Medicine
  • Biomedical Engineering

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  • Cite this

    Tseng, J. C., Levin, B., Hurtado, A., Yee, H., De Castro, I. P., Jimenez, M., Shamamian, P., Jin, R., Novick, R. P., Pellicer, A., & Meruelo, D. (2004). Systemic tumor targeting and killing by Sindbis viral vectors. Nature biotechnology, 22(1), 70-77. https://doi.org/10.1038/nbt917