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Gastrimmune raises antibodies that neutralize amidated and glycine-extended gastrin-17 and inhibit the growth of colon cancer.

Abstract
The effect of gastrin neutralization was evaluated on the in vivo growth of the rat colon line, DHDK12, which expressed cholecystokinin B/gastrin receptors and secreted glycine-extended gastrin-17 (G17). Gastrin neutralization was achieved by administration of the immunogen, Gastrimmune, which is composed of the amino terminal portion of G17 linked to a diphtheria toxoid. A rat-specific version of Gastrimmune was used to preimmunize rats, with control animals receiving diphtheria toxoid only. The antibodies raised neutralized both carboxy-amidated and glycine-extended G17. The tumor was implanted into the muscle layer of the abdominal wall, and rats immunized with Gastrimmune had significantly reduced median cross-sectional tumor areas (70.2% reduction; P = 0.005) and weights (56.5% reduction; P = 0.0078)) when compared to control rats. Histological analysis revealed that the tumors had an enhanced 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 inhibited the growth of a rat colon tumor. This could have been mediated by neutralization of both serum G17 and cell-associated precursor gastrin molecules.
AuthorsS A Watson, D Michaeli, S Grimes, T M Morris, G Robinson, A Varro, T A Justin, J D Hardcastle
JournalCancer research (Cancer Res) Vol. 56 Issue 4 Pg. 880-5 (Feb 15 1996) ISSN: 0008-5472 [Print] United States
PMID8631028 (Publication Type: Journal Article)
Chemical References
  • Cancer Vaccines
  • Diphtheria Toxoid
  • Gastrins
  • Immunoglobulin Isotypes
  • Immunotoxins
  • Receptor, Cholecystokinin B
  • Receptors, Cholecystokinin
  • gastrin immunogen
  • glycine-extended gastrin 17
Topics
  • Amino Acid Sequence
  • Animals
  • Antibody Formation
  • Antigen-Antibody Reactions
  • Cancer Vaccines
  • Cell Division
  • Colonic Neoplasms (pathology, therapy)
  • Diphtheria Toxoid (immunology, therapeutic use)
  • Drug Design
  • Gastrins (biosynthesis, immunology, therapeutic use)
  • Humans
  • Immunoglobulin Isotypes (biosynthesis)
  • Immunotoxins (therapeutic use)
  • Male
  • Molecular Sequence Data
  • Rabbits
  • Rats
  • Rats, Inbred Strains
  • Receptor, Cholecystokinin B
  • Receptors, Cholecystokinin (biosynthesis)

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