GASTRIMMUNE RAISES ANTIBODIES THAT NEUTRALIZE AMIDATED AND GLYCINE-EXTENDED GASTRIN-17 AND INHIBIT THE GROWTH OF COLON-CANCER

The effect of gastrin neutralization was evaluated on the in vivo grow th of the rat colon line, DHDK12, which expressed cholecystokinin B/ga strin receptors and secreted glycine-extended gastrin-17 (G17). Gastri n neutralization was achieved by administration of the immunogen, Gast rimmune, which is composed of the amino terminal portion of G17 linked to a diphtheria toroid. A rat-specific version of Gastrimmune was use d to preimnunize rats, with control animals receiving diphtheria toroi d only. The antibodies raised neutralized both carboxy-amidated and gl ycine-extended G17. The tumor was implanted into the muscle layer of t he abdominal mail, and rats immunized with Gastrimmune had significant ly reduced median cross-sectional tumor areas (70.2% reduction; P = 0. 005) and weights (56.5% reduction; P = 0.0078)) when compared to contr ol rats. Histological analysis revealed that the tumors had an enhance d degree of necrosis, with the area of viable tumor in the Gastrimmune -immunized rat reduced to 40.3% compared to 58.6% in the control rats (P = 0.003). Immunization with Gastrimmune raised antibodies that inhi bited the growth of a rat colon tumor. This could have been mediated b y neutralization of both serum G17 and cell-associated precursor gastr in molecules.