A comparison of an anti-gastrin antibody and cytotoxic drugs in the therapy of human gastric ascites in SCID mice

The therapeutic effect of antibodies raised by the immunogen Gastrimmune wa s compared with both a CCKB/gastrin receptor antagonist, CI-988, and 5-Fluo rouracil/leucovorin in a gastric cancer model. The human gastric ascites ce ll line, MGLVAIasc, produced and secreted progastrin and glycine-extended g astrin as determined by radioimmunoassay and immunocytochemistry, Cells wer e also stained with an antiserum directed against the human CCKB/gastrin re ceptor, MGLVAIasc cells were injected i.p. into SCID mice, Antibodies raise d by Gastrimmune immunization of rabbits (affinity for G17 of 0.15 nM and G lyG17 of 0.47 nM) were passively Infused i,p. and significantly enhanced su rvival by up to 5 days (p=0.0024 from vehicle controls). The enhancement in survival was not significantly different from that achieved by treatment w ith 5-Fruorouracil and leucovorin, A CCKB/gastrin receptor antagonist, CI-9 88, did not affect survival with cells injected at 7.5 x 10(5) cells/mouse but significantly increased the survival of mice injected with a lower cell innoculum of 5 x 10(5) cells/mouse from 30 to 35 days (p = 0.0186). At thi s lower innoculum antibodies raised by Gastrimmune induced complete surviva l in 2 animals with the remaining dead by day 36 (p = 0.0022). Thus, both e ndocrine and autocrine pathways mediated by precursor and mature gastrin mo lecules may be jointly operational in the gastric cancer scenario and may b e important targets for therapeutic agents. Int J. Cancer 81:248-254, 1999, (C) 1999 Wiley-Liss. Inc.