Anti-gonadotrophin releasing hormone antibodies inhibit the growth of MCF7 human breast cancer xenografts

Abstract

The human breast cancer cell line (MCF7) was established as xenografts in intact female nude mice. Xenografts did not require oestrogen supplementation for growth, although oestrogen supplementation caused more rapid tumour growth. GnRH Pharmaccine is an immunogen composed of gonadotrophin releasing hormone (GnRH) linked to diphtheria toxoid. Anti-GnRH antibodies purified from the serum of rabbits immunized with GnRH Pharmaccine, were used to passively immunize nude mice. In mice treated with anti-GnRH antibodies, xenograft growth was significantly inhibited relative to controls (median times of 71 and 29 days respectively taken for tumours to attain a predetermined cross-sectional area of 200 mm2, P < 0.001). The inhibition of tumour growth achieved by anti-GnRH antibodies was not significantly different from that produced by the anti-oestrogen, tamoxifen (59 days). Ovarian/uterine weights were reduced by 61% (P < 0.001) in anti-GnRH antibody-treated animals compared with controls. Histologically there was underdevelopment and atrophy of the reproductive organs. Serum levels of both oestrogen and luteinizing hormone were reduced by treatment with anti-GnRH antibodies (to 24.9% and 53% respectively of levels in controls, both P = 0.04). It is postulated that one of the mechanisms by which anti-GnRH antibody treatment inhibits tumour growth is indirectly, by reducing serum oestrogen levels.