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

123 Citations (Scopus)

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 2004
Externally publishedYes

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Tumors
Neoplasms
Cells
Gene therapy
Neoplasm Genes
Genetic Therapy
Carcinogens
Immunohistochemistry
Blood
Genes
Lung
Infection

ASJC Scopus subject areas

  • Microbiology

Cite this

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

Systemic tumor targeting and killing by Sindbis viral vectors. / Tseng, Jen Chieh; Levin, Brandi; Hurtado, Alicia; Yee, Herman; De Castro, Ignacio Perez; Jimenez, Maria; Shamamian, Peter; Jin, Ruzhong; Novick, Richard P.; Pellicer, Angel; Meruelo, Daniel.

In: Nature Biotechnology, Vol. 22, No. 1, 01.2004, p. 70-77.

Research output: Contribution to journalArticle

Tseng, JC, Levin, B, Hurtado, A, Yee, H, De Castro, IP, Jimenez, M, Shamamian, P, Jin, R, Novick, RP, Pellicer, A & Meruelo, D 2004, 'Systemic tumor targeting and killing by Sindbis viral vectors', Nature Biotechnology, vol. 22, no. 1, pp. 70-77. https://doi.org/10.1038/nbt917
Tseng JC, Levin B, Hurtado A, Yee H, De Castro IP, Jimenez M et al. Systemic tumor targeting and killing by Sindbis viral vectors. Nature Biotechnology. 2004 Jan;22(1):70-77. https://doi.org/10.1038/nbt917
Tseng, Jen Chieh ; Levin, Brandi ; Hurtado, Alicia ; Yee, Herman ; De Castro, Ignacio Perez ; Jimenez, Maria ; Shamamian, Peter ; Jin, Ruzhong ; Novick, Richard P. ; Pellicer, Angel ; Meruelo, Daniel. / Systemic tumor targeting and killing by Sindbis viral vectors. In: Nature Biotechnology. 2004 ; Vol. 22, No. 1. pp. 70-77.
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