The therapeutic potential of a tumor-specific IgE antibody in ovarian cancer

SN Karagiannis PhD^a, MG Bracher BSc^a, Q Wang PhD^a, N East BSc^b, RG Thompson BSc^b, F Burke PhD^b, FR Balkwill PhD^b, HJ Gould PhD^a

^aGKT School of Biomedical Sciences, King's College London, The Randall Centre, London, United Kingdom, ^bICRF Translational Oncology Laboratory, Queen Mary’s School of Medicine & Dentistry, Bart's and The London, London, United Kingdom

AIM: We investigated the ability of chimeric MOv18 IgE to target tumor cells and suppress tumor growth both in vitro and in vivo. We identified the cytotoxic cells involved in tumour targeting and attempted to gain some insight into the killing mechanisms involved. METHODS: Peripheral blood mononuclear cells (PBMCs) were purified by Histopaque gradient centrifugation from venous blood of healthy volunteers. MOv18 IgE-mediated cytotoxicity (ADCC) of blood effector cells against human ovarian carcinoma cell line IGROV1 was examined by lactate dehydrogenease release (LDH) assay and by a dual-colour flow cytometric (FACS) method using a live/dead cytotoxicity kit. Targeting of MOv18 IgE and PBMCs to human ovarian carcinoma in vivo was performed in HUA tumour xenografts grown i.p. in nu/nu mice. RESULTS: We demonstrated that chimeric IgE antibody against the folic acid receptor (MOv18 IgE) inhibits tumor growth in a nude-mouse model of ovarian carcinoma. MOv18 IgE gave greater protection than the corresponding chimeric MOv18 IgG1. Human monocytes were active in IgE antibody-dependent cell-mediated cytotoxicity. Injection of tumor-bearing nude mice with PBMC and MOv18 IgE led to infiltration of monocytes into the tumors and prolonged survival of the mice. Incubation of PBMC or purified monocytes and MOv18 IgE with ovarian tumor cells in vitro resulted in tumor cell killing proportional to the expression of unoccupied Fcepsilon RI on monocytes. We observed phagocytosis of tumor cells by the monocytes in vitro. CONCLUSION: Our data suggest that the allergic reaction induced by IgE antibodies to tumour antigens may be harnessed for the suppression of ovarian cancer. We postulate that tumour antigen-specific IgE can be a potential therapeutic tool in the treatment of malignancies.

Paper presented at the International Symposium on Predictive Oncology and Intervention Strategies; Nice, France; February 7 - 10, 2004; in oral session 995 (Immunotherapy).