Interleukin-2: hope in cases of cisplatin-resistant tumours |
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| Authors: | Monique R Bernsen Alike W Van Der Velden Linda A Everse Hub F J Dullens Willem Den Otter A Peter M Heintz |
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| Institution: | (1) Department of Functional Morphology, Faculty of Veterinary Medicine, Utrecht University, Utrecht, The Netherlands, NL;(2) Department of Obstetrics and Gynecology, University of Utrecht Hospital, Utrecht, The Netherlands, NL;(3) Department of Pathology, University of Utrecht Hospital, Utrecht, The Netherlands, NL;(4) Department of Pathology, University Hospital Nijmegen, P.O. Box 9101, 6500 HB Nijmegen, The Netherlands Tel. +31 24 361 4368 Fax: +31 24 354 0520 e-mail: m.bernsen@pathol.azn.nl, NL |
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| Abstract: | To establish whether or not local low-dose recombinant interleukin-2 (rIL-2) therapy might result in therapeutic benefit
for ovarian cancer patients treated with cisplatin, the antitumour effects of rIL-2 and of combined treatment with cisplatin
and rIL-2 in a mouse ovarian tumour (MOT) model were studied. In addition, some possible mechanistic aspects underlying the
observed antitumour responses were analysed. MOT cells were injected i.p. into syngeneic, immunocompetent, female C3HeB mice.
Tumour-bearing mice received i.p. treatment with cisplatin, rIL-2 or both. The MOT tumour appeared to be hardly responsive
to treatment with cisplatin only or rIL-2 only. In contrast, combined local treatment with low doses of cisplatin (1 and 5
mg/kg body weight) and rIL-2 (60 000 U/day) resulted in an effective antitumour response in MOT-bearing mice. Complete rejection
of the i.p. (local) tumour occurred in up to 60% of the cases. In vitro studies showed that cisplatin and rIL-2 do not have
cumulative direct toxic effects on MOT cells. Mice cured after combined treatment with cisplatin and rIL-2 were not able to
reject a rechallenge with tumour cells, indicating that these mice had not developed immunity to the tumour. Analysis of tumour-associated
leucocytes, however, showed that combined treatment with cisplatin and rIL-2 did result in enhanced non-specific cytolytic
activity of peritoneal leucocytes. We have thus demonstrated that, in the MOT model, combined local treatment with low doses
of cisplatin and of rIL-2 is far more effective than therapy with cisplatin alone. Non-specific cytotoxicity of leucocytes
appears to be involved in antitumour responses induced by combined treatment with cisplatin and rIL-2. These results suggest
that, in human ovarian carcinoma, much better results may be obtained with the combined treatment of cisplatin and low (non-toxic)
doses of rIL-2 than with cisplatin only. This may also apply to cisplatin-resistant ovarian carcinoma.
Received: 6 March 1997 / Accepted: 30 October 1997 |
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| Keywords: | Cisplatin Interleukin-2 Chemo-immunotherapy Ovarian tumour model |
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