Pre-clinical evaluation of the Gastrimmune immunogen alone and in combination with 5-fluorouracil/leucovorin in a rat colorectal cancer model

✍ Scribed by Susan A. Watson; Dov Michael; Timothy A. Justin; Stephen Grimes; Teresa M. Morris; Graham Robinson; Philip A. Clarke; Jack D. Hardcastle

• Publisher: John Wiley and Sons
• Year: 1998
• Tongue: French
• Weight: 135 KB
• Volume: 75
• Category: Article
• ISSN: 0020-7136
• DOI: 10.1002/(sici)1097-0215(19980316)75:6<873::aid-ijc9>3.0.co;2-s

✦ Synopsis

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 g • 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 g • 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.