Effects of Tumour Necrosis Factor on Human Tumour Xenografts in Nude Mice

  1. Gregory Bock Organizer and
  2. Joan Marsh
  1. F. R. Balkwill1,
  2. B. G. Ward1 and
  3. W. Fiers2

Published Online: 28 SEP 2007

DOI: 10.1002/9780470513521.ch11

Ciba Foundation Symposium 131 - Tumour Necrosis Factor and Related Cytotoxins

Ciba Foundation Symposium 131 - Tumour Necrosis Factor and Related Cytotoxins

How to Cite

Balkwill, F. R., Ward, B. G. and Fiers, W. (2007) Effects of Tumour Necrosis Factor on Human Tumour Xenografts in Nude Mice, in Ciba Foundation Symposium 131 - Tumour Necrosis Factor and Related Cytotoxins (eds G. Bock and J. Marsh), John Wiley & Sons, Ltd., Chichester, UK. doi: 10.1002/9780470513521.ch11

Author Information

  1. 1

    Imperial Cancer Research Fund, P.O. Box No. 123, Lincoln's Inn Fields, London WC2A 3PX, UK

  2. 2

    Laboratory for Molecular Biology, State University of Gent, K L Ledeganckstraat 35, B-9000 Gent, Belgium

Publication History

  1. Published Online: 28 SEP 2007

ISBN Information

Print ISBN: 9780471910978

Online ISBN: 9780470513521

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Keywords:

  • tumour necrosis factor;
  • human tumour xenografts;
  • nude mice;
  • human ovarian tumours;
  • solid tumours

Summary

Recombinant human tumour necrosis factor (rHuTNF) when injected intraperitoneally into nude mice bearing subcutaneous tumour xenografts (breast and bowel) had no significant antitumour activity (six different tumours were tested). The same dose administered locally at the tumour site resulted in complete regression and cure of the majority of tumours. Macroscopic evidence of tumour necrosis was rarely seen but microscopically a peritumoral cuff of host inflammatory cells surrounded the dying tumour cells within four days of the start of therapy. The combination of rHuTNF (i.p.) with recombinant human γ-interferon (rHuIFN-γ) (i.p.) led to significant tumour inhibition in only one of three xenografts tested. Combination of rHuTNF (i.p.) and HuIFN-α (s.c.) resulted in significant inhibition in all of three xenografts tested.

Human ovarian tumours were grown in the peritoneal cavity of nude nice. The biological behaviour of this cancer closely resembled the human disease, the xenografts growing as solid tumours and/or ascites. When rHuTNF or rHuIFN-γ were given intraperitoneally at the time of tumour cell injection most mice survived, whereas control mice died in 4–8 weeks. Once the disease was established (seven days or more after injection) either agent alone was ineffective. In the combined results of three experiments with one xenograft, with a total of 21 mice in each group, cumulative survival at 154 days was 0% for control mice and 5% and 15% for mice treated with 1 µg/day rHuTNF or 5 × 104 U/day rHuIFN-γ, respectively, when therapy was started seven days after tumour cell injection. Combining the two agents led to a cumulative survival of 85%. This combination cured 40% of mice by 21 days after tumour cell injection. With a further two ovarian cancer xenografts, the combination of rHuTNF and rHuIFN-γ produced a significant survival advantage.