Antibodies raised by Gastrimmune inhibit the spontaneous metastasis of a human colorectal tumour, AP5LV

Both precursor forms of gastrin and mature amidated gastrin peptides can en hance proliferation of colorectal tumours and may regulate growth in an aut ocrine manner. The purpose of this study was to evaluate the effect of neut ralisation of precursor and amidated gastrin on primary and secondary in vi vo growth of a human colorectal tumour. The human colorectal cell line, AP5 LV, when injected into the muscle layer of the abdominal wall of severe com bined immunodeficient (SCID) mice, grows as a well-vascularised primary tum our and metastasise's to the lung. AP5LV expressed the precursor gastrin fo rms; progastrin and glycine-extended gastrin and gastrin/CCKB receptors, as assessed by immunocytochemistry. Gastrimmune is a gastrin immunogen in whi ch the amino terminus of the gastrin-17 molecule is linked to diphtheria to roid and induces antibodies which neutralise the amidated and glycine-exten ded forms of gastrin-17. Rabbit antiserum, raised against Gastrimmune, was administered intravenously into SCID mice bearing AP5LV tumours. Control an imals were treated with antiserum raised against diphtheria toroid only. An tibodies raised against Gastrimmune significantly limited the growth of pri mary AP5LV tumours, as assessed by median cross-sectional area (controls = 244mm(2); antibody-treated = 179 mm(2); P=0.033). In addition Gastrimmune-i nduced antiserum limited the growth of lung metastasis as assessed by nodul e number (controls = 3.5; antibody-treated=1.0; P=0.0001) and nodule cross- sectional as assessed by image analysis (controls 11.9 mm(2); antibody-trea ted=3.75mm(2); P=0.0064). In conclusion in vivo neutralisation of gastrin f orms, which may potentially be fuelling growth by an autocrine pathway, inh ibited both primary growth and, to a greater degree, lung metastasis of a h uman colorectal tumour cell line. Immunisation against tumour-associated ga strin forms may provide an effective therapy for advanced colorectal cancer . (C) 1999 Elsevier Science Ltd. All rights reserved.