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Systemic vector leakage and transgene expression by intratumorally injected recombinant adenovirus vectors.

Publication ,  Journal Article
Lohr, F; Huang, Q; Hu, K; Dewhirst, MW; Li, CY
Published in: Clin Cancer Res
November 2001

Interleukin 12 is a heterodimeric cytokine that exhibits potent immunostimulatory effects. It has shown some promise in preclinical and clinical studies but was accompanied by serious systemic toxicity such as flu-like syndromes, a rapid transient leukopenia, elevated liver transaminases, gastrointestinal toxicity, and/or liver dysfunction. Gene therapy with intratumorally injected recombinant adenoviral vectors offers the potential to restrict therapeutic gene expression in the tumor. Here we show that a substantial amount of adenoviral vectors disseminates into the systemic circulation and infects parenchymal organs. We further show that this results in high systemic levels of potentially toxic transgene products. To reduce potential toxicity, we tested an inducible promoter based on the heat shock proteins (hsp70B) and present evidence that high intratumoral levels of a therapeutic transgene can be obtained while systemic expression is reduced to a minimum, increasing the safety of adenovirus-based tumor gene therapy.

Duke Scholars

Published In

Clin Cancer Res

ISSN

1078-0432

Publication Date

November 2001

Volume

7

Issue

11

Start / End Page

3625 / 3628

Location

United States

Related Subject Headings

  • Tumor Cells, Cultured
  • Transgenes
  • Spleen
  • Promoter Regions, Genetic
  • Oncology & Carcinogenesis
  • Neoplasms, Experimental
  • Mice, Inbred C57BL
  • Mice, Inbred BALB C
  • Mice
  • Liver
 

Citation

APA
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MLA
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Lohr, F., Huang, Q., Hu, K., Dewhirst, M. W., & Li, C. Y. (2001). Systemic vector leakage and transgene expression by intratumorally injected recombinant adenovirus vectors. Clin Cancer Res, 7(11), 3625–3628.
Lohr, F., Q. Huang, K. Hu, M. W. Dewhirst, and C. Y. Li. “Systemic vector leakage and transgene expression by intratumorally injected recombinant adenovirus vectors.Clin Cancer Res 7, no. 11 (November 2001): 3625–28.
Lohr F, Huang Q, Hu K, Dewhirst MW, Li CY. Systemic vector leakage and transgene expression by intratumorally injected recombinant adenovirus vectors. Clin Cancer Res. 2001 Nov;7(11):3625–8.
Lohr, F., et al. “Systemic vector leakage and transgene expression by intratumorally injected recombinant adenovirus vectors.Clin Cancer Res, vol. 7, no. 11, Nov. 2001, pp. 3625–28.
Lohr F, Huang Q, Hu K, Dewhirst MW, Li CY. Systemic vector leakage and transgene expression by intratumorally injected recombinant adenovirus vectors. Clin Cancer Res. 2001 Nov;7(11):3625–3628.

Published In

Clin Cancer Res

ISSN

1078-0432

Publication Date

November 2001

Volume

7

Issue

11

Start / End Page

3625 / 3628

Location

United States

Related Subject Headings

  • Tumor Cells, Cultured
  • Transgenes
  • Spleen
  • Promoter Regions, Genetic
  • Oncology & Carcinogenesis
  • Neoplasms, Experimental
  • Mice, Inbred C57BL
  • Mice, Inbred BALB C
  • Mice
  • Liver