1. Biotechnology Center, Department of Pharmacy, Fourth Military Medical University, Xian, China;
2. National Institutes for Food and Drug Control, Beijing, China;
3. OnkoRx Ltd., Beijing, China.
The objective of this study was to determine the effect of anti-gastrin antiserum in combination with varied dosages of cytotoxic drugs (5-Fluorouracil (5FU) + Cisplatin (CDDP)) in vivo growth of the human gastric cancer cell-line, SGC-7901, which expressed cholecystokininB/gastrin receptors and secreted gastrin. The anti-gastrin antiserum was obtained by immunizing rabbits using a novel immunogen vaccine, which was composed of the common amino-terminal portion of human carboxy-amidated gastrin-17 (G17) and glycine-extended gastrin-17 (gly-G17) and the common carboxy-terminal portion of progastrin (in a 50:50 mixture) all covalently linked to tetanus toxoid (TT) by specific peptide spacers. The antiserum neutralized both G17 and gly-G17 by enzyme-linked immunosorbent assay (ELISA), and a synthetic progastrin peptide, as well, using an E. coli expressed his-tagged progastrin.
The tumor was implanted subcutaneously into the backside of BALB/c nude mice, and the combination antibody-drug treatment using low dose combination chemotherapy had significantly reduced median tumor volumes (62% reduction; p =0.0018) and tumor weights (53% reduction; p =0.0062) when compared to the conventional high dose chemotherapy treated control mice that had a corresponding similar reductive effect, using just the two standard cytotoxic drugs alone; namely by reducing the tumor volumes (65%; p =0.0016) and tumor weights (59% reduction; p=0.0033). Importantly, the immunological treatment had little of the toxicities and side-effects of the full chemotherapy doses alone, which was effected by using a significant decrease in the dosage of chemotherapeutic drugs, while maintaining the same level of efficacy at reduction of tumor growth.
Keywords: Gastrins, Progastrin, Cancer, Cytotoxic Drugs, Antibody.