Author/Authors :
A. D. Gilliam، نويسنده , , S. A. Watson، نويسنده , , M. Henwood، نويسنده , , A. J. McKenzie، نويسنده , , J. E. Humphreys، نويسنده , , Randal J. Elder، نويسنده , , S. Y. Iftikhar، نويسنده , , N. Welch، نويسنده , , J. Fielding، نويسنده , , P. Broome، نويسنده , , D. Michaeli، نويسنده ,
Abstract :
Purpose. G17DT is a gastrin immunogen, raising antibodies that blockade gastrin-stimulated growth. The aim of the study was to characterise antibody response and assess safety and tolerability of G17DT given to patients with gastric cancer.
Experimental design. G17DT was administered to 52 patients with gastric adenocarcinoma at weeks 0, 2 and 6 by intramuscular injection at doses of 10, 100 and 250 μg. Antibody levels were measured by an ELISA assay.
A radioligand displacement assay determined the ability of G17DT-immunised patientsʹ sera to inhibit binding of 125IG17 to cholecystokinin (CCK)-2 receptors.
Results. By week 12 of the study, 6/12 evaluable stage I–III patients achieved an antibody response in the 10 μg group, 7/11 in the 100 μg group, and 11/12 in the 250 μg group. Stage IV patients dosed at 250 μg achieved a similar response rate to stage I–III patients dosed at 10 or 100 μg. G17DT was well tolerated in 47/52 patients. Two patients suffered significant adverse reactions including injection site pain and abscess.
G17DT antibodies displaced iodinated gastrin from CCK-2 receptors, with the level of displacement correlating with antibody titre.
Conclusions. G17DT immunisation is a well-tolerated method of raising functional antibodies to 17 amino acid gastrin forms in patients with gastric carcinomas.
