1. ¹Department of Bacteriology and Immunology, Haartman Institute, University of Helsinki, FIN-00014 Helsinki, Finland
2. ²Department of Obstetrics and Gynaecology, N-5021 Haukeland Hospital, University of Bergen, Norway
3. ³Department of Microbiology and Immunology, The Gade Institute, Haukeland University Hospital, N-5021 Bergen, Norway
4. ⁴Department of Pathology, The Gade Institute, Haukeland University Hospital, N-5021 Bergen, Norway
5. ⁵Huslab, Helsinki University Central Hospital, FIN-00290 Helsinki, Finland

Correspondence: Dr L Bjørge, Department of Obstetrics and Gynaecology, Haukeland University Hospital, N-5021 Bergen, Norway. E-mail: Line.Bjorge@gades.uib.no

Revised 8 November 2004; Accepted 22 November 2004; Published online 22 February 2005.

Abstract

Ovarian cancer spreads intraperitoneally and forms fluid, whereby the diagnosis and therapy often become delayed. As the complement (C) system may provide a cytotoxic effector arm for both immunological surveillance and mAb-therapy, we have characterised the C system in the intraperitoneal ascitic fluid (AF) from ovarian cancer patients. Most of the AF samples showed alternative and classical pathway haemolytic activity. The levels of C3 and C4 were similar to or in the lower normal range when compared to values in normal sera, respectively. However, elevated levels of C3a and soluble C5b-9 suggested C activation in vivo. Malignant cells isolated from the AF samples had surface deposits of C1q and C3 activation products, but not of C5b-9 (the membrane attack complex; MAC). Activation could have become initiated by anti-tumour cell antibodies that were detected in the AFs and/or by changes on tumour cell surfaces. The lack of MAC was probably due to the expression of C membrane regulators CD46, CD55 and CD59 on the tumour cells. Soluble forms of C1 inhibitor, CD59 and CD46, and the alternative pathway inhibitors factor H and FHL-1 were present in the AF at concentrations higher than in serum samples. Despite the presence of soluble C inhibitors it was possible to use AF as a C source in antibody-initiated killing of ovarian carcinoma cells. These results demonstrate that although the ovarian ascitic C system fails as an effective immunological surveillance mechanism, it could be utilised as an effector mechanism in therapy with intraperitoneally administrated mAbs, especially if the intrinsic C regulators are neutralised.