Gastrimmune-induced antigastrin-17 antibodies inhibit acid secretion in a rat fistula model.
BACKGROUND
Gastrimmune is an immunogenic form of gastrin. It raises in situ antibodies against two proliferative forms of gastrin: amidated and glycine-extended gastrin-17. It has been shown to have a therapeutic action in several in vivo tumour models. Following immunization, due to the complex equilibrium that exists between the antibodies and gastrin, it is not technically feasible to assay for free gastrin.


OBJECTIVE
To determine the effect of Gastrimmune-induced antigastrin antibodies on acid secretion.


METHODS
A rat gastric fistula model was used. Animals (six per group) were immunized with a control immunogen or ascending doses of Gastrimmune. Acid output was measured following infusion of increasing doses of gastrin-17 and pentagastrin.


RESULTS
Gastrimmune-induced antibodies significantly reduced gastrin-17-stimulated acid output compared to control animals (Gastrimmune at 200 microg/rat vs. control; acid output following 30 ng gastrin-17, 0.01 vs. 0.16, P < 0.001; following 120 ng gastrin-17, 0.022 vs. 0.29, P < 0.001).


CONCLUSIONS
Gastrimmune significantly inhibits gastrin-17-stimulated acid output. This biological assay suggests that the antigastrin antibodies effectively bind gastrin-17. In addition to its use as an antineoplastic agent, Gastrimmune may have a role as an acid-decreasing agent in oesophagogastric pathology.
Smith
A M
AM
The Academic Unit of Cancer Studies, University Hospital, Nottingham, UK.
Morris
T
T
Justin
T
T
Michaeli
D
D
Watson
S A
SA
D000818:Animals; D000906:Antibodies / Q000494:pharmacology*; D019496:Cancer Vaccines; D004168:Diphtheria Toxoid / Q000494:pharmacology*; D004195:Disease Models, Animal; D005260:Female; D005744:Gastric Acid / Q000378:metabolism*; D005747:Gastric Fistula / Q000378:metabolism*; D005755:Gastrins / Q000276:immunology* / Q000494:pharmacology*; D005765:Gastrointestinal Agents / Q000494:pharmacology; D007114:Immunization; D008297:Male; D010418:Pentagastrin / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar
D000906:Antibodies; D019496:Cancer Vaccines; D004168:Diphtheria Toxoid; D005755:Gastrins; D005765:Gastrointestinal Agents; C482698:gastrin immunogen; C013550:gastrin 17; D010418:Pentagastrin