Gastrimmune raises antibodies that neutralize amidated and glycine-extended gastrin-17 and inhibit the growth of colon cancer.
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.
Watson
S A
SA
Department of Surgery, Queen's Medical Centre, University of Nottingham, United Kingdom.
Michaeli
D
D
Grimes
S
S
Morris
T M
TM
Robinson
G
G
Varro
A
A
Justin
T A
TA
Hardcastle
J D
JD
D000595:Amino Acid Sequence; D000818:Animals; D000917:Antibody Formation; D000937:Antigen-Antibody Reactions; D019496:Cancer Vaccines; D002455:Cell Division; D003110:Colonic Neoplasms / Q000473:pathology* / Q000628:therapy*; D004168:Diphtheria Toxoid / Q000276:immunology / Q000627:therapeutic use*; D015195:Drug Design; D005755:Gastrins / Q000096:biosynthesis / Q000276:immunology* / Q000627:therapeutic use*; D006801:Humans; D007132:Immunoglobulin Isotypes / Q000096:biosynthesis; D000922:Immunotoxins / Q000627:therapeutic use*; D008297:Male; D008969:Molecular Sequence Data; D011817:Rabbits; D051381:Rats; D011919:Rats, Inbred Strains; D043887:Receptor, Cholecystokinin B; D011949:Receptors, Cholecystokinin / Q000096:biosynthesis
D019496:Cancer Vaccines; D004168:Diphtheria Toxoid; D005755:Gastrins; D007132:Immunoglobulin Isotypes; D000922:Immunotoxins; D043887:Receptor, Cholecystokinin B; D011949:Receptors, Cholecystokinin; C482698:gastrin immunogen; C086854:glycine-extended gastrin 17