Premium
Pre‐clinical evaluation of the Gastrimmune immunogen alone and in combination with 5‐fluorouracil/leucovorin in a rat colorectal cancer model
Author(s) -
Watson Susan A.,
Michael Dov,
Justin Timothy A.,
Grimes Stephen,
Morris Teresa M.,
Robinson Graham,
Clarke Philip A.,
Hardcastle Jack D.
Publication year - 1998
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/(sici)1097-0215(19980316)75:6<873::aid-ijc9>3.0.co;2-s
Subject(s) - immunogen , fluorouracil , antibody , in vivo , medicine , gastrin , colorectal cancer , gastroenterology , diphtheria toxin , chemotherapy , immunology , cancer , biology , monoclonal antibody , toxin , biochemistry , microbiology and biotechnology , secretion
Mature and post‐translational precursor gastrin forms are growth factors for colorectal tumours. The immunogen Gastrimmune is composed of the amino terminus of gastrin‐17 linked to diphtheria toxoid and raises antibodies in situ which neutralise amidated and glycine‐extended gastrin‐17. The aim of the study was to determine the effect of treatment with 5‐fluorouracil(5‐FU)/leucovorin on the antibody titres induced by Gastrimmune and the effect of combination therapy on the growth of the rat colon tumour DHDK12. Gastrimmune was administered to rats s.c. at 3 weekly intervals. The rat colon tumour line DHDK12 was injected into the abdominal wall of BDIX rats. Combinations of 5‐FU/leucovorin were injected i.v. on days 1, 3 and 5, with the cycle repeated every 4 weeks. Antibody titres were measured by an ELISA technique. Antibody titres were followed for 40 weeks after Gastrimmune (500 μg · ml −1 ) immunization, with titres peaking between 10 and 20 weeks after a single immunisation and falling by week 30. At termination, no effect was observed on either the histological appearance of the gastro‐intestinal tract or the proliferation of the colonic mucosa. Pre‐ and post‐treatment with 5‐FU/leucovorin (30 mg · kg −1 ) had no effect on the kinetics and level of antibody response to Gastrimmune. Gastrimmune (200 μg · ml −1 ) and 5‐FU/leucovorin combinations (12.5 and 20 mg · kg −1 ) increased the therapeutic effects on the in vivo growth of DHDK12 tumors when compared to the agents given singly. Gastrimmune immunisation may be a therapeutic option for the treatment of colorectal cancer in combination with 5‐FU/leucovorin. Int. J. Cancer 75:873–877, 1998. © 1998 Wiley‐Liss, Inc.