Differential kinetics for immunoneutralization of circulating gastrin by gastrin monoclonal antibody and its Fab1 fragment in rats.
The kinetics of gastrin immunoneutralization were studied in rats treated with a mouse monoclonal IgG antibody to gastrin (CURE GAS 93) and with the Fab1 prepared from this antibody. Clearance studies using specific ELISA measurements of serum IgG or Fab determined the T1/2 for IgG as 59.3 +/- 3.5 h and for Fab1 as 7.3 +/- 0.7 h. Gastrin was immunoneutralized in rats for up to 16 days using alternate day IP injections of anti-gastrin immunoglobulin. Gastric acid secretion stimulated by gastrin-17, but not histamine, was inhibited 48 h after the last dose of antibody, indicating specific inhibition of gastrin. Peak serum levels of antibody were observed 8 h after IP administration and indicated an estimated 70% absorption of the administered dose. Fab1 fragments completely blocked gastric acid secretion stimulated by gastrin-17, but not histamine, 4 h after IV administration; however, this effect was not observed 24 h after administration. This study demonstrates the effectiveness of chronic immunoneutralization of gastrin and defines the effective period of immunoneutralization for intact IgG and for the Fab1 fragment.
Ohning
G V
GV
Department of Veteran Affairs, West Los Angeles Medical Center, CA.
Wong
H C
HC
Walsh
J H
JH
D000818:Animals; D000911:Antibodies, Monoclonal; D000937:Antigen-Antibody Reactions; D005744:Gastric Acid / Q000378:metabolism; D005755:Gastrins / Q000097:blood* / Q000276:immunology; D007140:Immunoglobulin Fab Fragments / Q000097:blood*; D007074:Immunoglobulin G / Q000097:blood; D007274:Injections, Intraperitoneal; D007275:Injections, Intravenous; D007700:Kinetics; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley
D000911:Antibodies, Monoclonal; D005755:Gastrins; D007140:Immunoglobulin Fab Fragments; D007074:Immunoglobulin G