The protective role of IgE in ovarian carcinoma.

SN Karagiannis, PhDa Q Wang, PhDa, N East, BScb, F Burke, PhDb, FR Balkwill, PhDb and HJ Gould, PhDa

aThe Randall Centre, GKT School of Biomedical Sciences, London, United Kingdom bICRF Translational Oncology Laboratory, St Bartholomew's and The Royal London School of Medicine & Dentistry, London, United Kingdom

Aims: We investigate the efficacy of chimeric MOv18 IgE antibody against ovarian tumour antigen Folate Binding Protein in suppressing tumour growth. We examine the cytotoxic cells involved in tumour targeting and the killing mechanisms involved. Methods: We have constructed chimeric IgE antibody with murine V regions and human C regions. MOv18 IgE-mediated cytotoxicity (ADCC) of human ovarian carcinoma IGROV1 cells was examined by dual-stain flow cytometric and lactate dehydrogenease release (LDH) assays. Targeting of MOv18 IgE and peripheral blood mononuclear cells (PBMC) to human ovarian carcinoma in vivo was performed in HUA tumour xenografts grown i.p. in nu/nu mice. Results: Mice injected with PBMC and MOv18 IgE survived longer (40 days) than mice given PBMCs alone (30 days) or controls (22 days). In vitro assays show that PBMCs from normal donors induce MOv18 IgE-specific killing more effectively (23-29%) than PBMCs from allergic patients (7-14%). Normal PBMCs have a higher proportion of monocytes expressing unoccupied Fcε RI compared to allergic PBMCs. Therefore, IgE ADCC appears dependent on exposure of free IgE receptor on cytotoxic cells. Monocytes and basophils, both bearing IgE receptors, contact ovarian tumour cells by 15 minutes, promoting lysis and structural disintegration of the target cells by 3 hours. Human macrophages infiltrate tumours in HUA xenografts in mice treated with MOv18 IgE. Conclusions: We show that IgE and immune cells mediate cytotoxic killing of ovarian carcinoma in vitro and in vivo. The allergic reaction induced by IgE antibodies to tumour antigens may therefore be harnessed for the suppression of ovarian cancer.

KEY WORDS: Chimeric MOv18 IgE, Folate Binding Protein, monocytes, ovarian carcinoma, Fc&epsilon, .

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Paper presented at the International Symposium on Predictive Oncology and Intervention Strategies; Paris, France; February 9 - 12, 2002; in the section on Immunotherapy.