A comparison of the therapeutic effectiveness of gastrin neutralisation intwo human gastric cancer models: relation to endocrine and autocrine/paracrine gastrin mediated growth

Background-Gastrin is a growth factor for established tumours. Aims-To inve stigate the therapeutic effect of antibodies, raised against the Gastrimmun e immunogen, which neutralise the glycine extended and carboxy amidated for ms of gastrin 17 in two human gastric cancer models. Methods-MGLVA1 cells (which have a gastrin autocrine/paracrine phenotype) a nd ST16 cells (which have an endocrine phenotype) were injected into the pe ritoneal cavity of SCID mice. Peritoneal tumours, ascites, and cachexia for mation occurred, with the monitored endpoint being morbidity. Results-In MGLVA1 cells, intravenous administration of antibodies raised ag ainst Gastrimmune increased the 50% median survived by 25% at three differe nt initial cell seeding concentrations (1 x 10(6)-5 x 10(5) per mouse). In ST16 cells, the effect of Gastrimmune induced antibodies on time to morbidi ty was greatest at the lowest cell seeding concentration (5 x 10(5) cells/m ouse) with the 50% median survival increased by 74% and overall survival ac hieved in 38% of the mice. Conclusions-Gastrimmune may have potential therapeutic benefit on gastrin s ensitive gastric tumours and may interact with both endocrine and autocrine mediated growth pathways.