Sa. Watson et al., GASTRIMMUNE RAISES ANTIBODIES THAT NEUTRALIZE AMIDATED AND GLYCINE-EXTENDED GASTRIN-17 AND INHIBIT THE GROWTH OF COLON-CANCER, Cancer research, 56(4), 1996, pp. 880-885
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.