Tumour therapy in mice using adenovirus vectors expressing human TNFa.

  • Authors:
    • R A Marr
    • M Hitt
    • W J Muller
    • J Gauldie
    • F L Graham
  • View Affiliations

  • Published online on: March 1, 1998     https://doi.org/10.3892/ijo.12.3.509
  • Pages: 509-524
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Abstract

Induction of systemic toxicity is a major factor limiting the use of TNFa in tumour therapy. The local expression of TNFa from Ad vector infected tumour cells, might result in reduced systemic toxicity and induce an enhanced local antitumour response. Two adenoviral vectors expressing human TNFa were constructed for use in tumour immunotherapy, one utilizing the HCMV promoter (Ad-HCMV-TNF) and the second utilizing the MCMV promoter (Ad-MCMV-TNF). Both vectors induced the secretion of hTNFa from transduced cells in vitro, however the MCMV promoter directed stronger expression in murine cells. Expression from the two vectors was also kinetically different with the MCMV promoter inducing earlier expression, from murine tumour cells in vitro and in vivo. Both vectors induced intratumoural necrosis, however only the Ad-MCMV-TNF vector induced systemic toxicity and significant antitumour activity when directly injected into tumours, killing 8 of 20 mice and inducing partial (2 of 12) and permanent (1 of 12) tumour regressions at a dose of 5x108 pfu/mouse. These data indicate that hTNFa expressed from an Ad vector is considerably toxic to mice while inducing a moderate antitumour response.

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Mar 1998
Volume 12 Issue 3

Print ISSN: 1019-6439
Online ISSN:1791-2423

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Spandidos Publications style
Marr R, Hitt M, Muller W, Gauldie J and Graham F: Tumour therapy in mice using adenovirus vectors expressing human TNFa.. Int J Oncol 12: 509-524, 1998
APA
Marr, R., Hitt, M., Muller, W., Gauldie, J., & Graham, F. (1998). Tumour therapy in mice using adenovirus vectors expressing human TNFa.. International Journal of Oncology, 12, 509-524. https://doi.org/10.3892/ijo.12.3.509
MLA
Marr, R., Hitt, M., Muller, W., Gauldie, J., Graham, F."Tumour therapy in mice using adenovirus vectors expressing human TNFa.". International Journal of Oncology 12.3 (1998): 509-524.
Chicago
Marr, R., Hitt, M., Muller, W., Gauldie, J., Graham, F."Tumour therapy in mice using adenovirus vectors expressing human TNFa.". International Journal of Oncology 12, no. 3 (1998): 509-524. https://doi.org/10.3892/ijo.12.3.509