Effects of genetic engineering on the pharmacokinetics of antibodies.
Monoclonal antibodies (MAbs) may be considered 'magic bullets' due to their ability to recognize and eradicate malignant cells. MAbs, however, have practical limitations for their rapid application in the clinics. The structure of antibody molecules can be engineered to modify functional domains such as antigen-binding sites and/or effector functions. Advances in genetic engineering have provided rapid progress in the development of new immunoglobulin constructs of MAbs with defined research and therapeutic application. Recombinant antibody constructs are being engineered, such as human-mouse chimeric, domain-dispositioned, domain-deleted, humanized and single-chain Fv fragments. Genetically-engineered antibodies differ in size and rate of catabolism. Pharmacokinetic studies show that the intact IgG (150 kD), enzymatically derived fragments Fab' (50 kD) and single chain Fv (28 kD) have different clearance rates. These antibody forms clear 50% from the blood pool in 2.1 days, 30 minutes and 10 minutes, respectively. Genetically-engineered antibodies make a new class of immunotherapeutic tracers for cancer treatment.
Colcher
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D
Department of Pathology and Microbiology, University of Nebraska Medical Center, Omaha 68198-3135, USA.
Goel
A
A
Pavlinkova
G
G
Beresford
G
G
Booth
B
B
Batra
S K
SK
D000230:Adenocarcinoma / Q000532:radiotherapy; D000818:Animals; D000911:Antibodies, Monoclonal / Q000235:genetics / Q000493:pharmacokinetics*; D000937:Antigen-Antibody Reactions; D001666:Binding Sites, Antibody / Q000235:genetics; D002678:Chimera / Q000235:genetics; D005818:Genetic Engineering; D006801:Humans; D007140:Immunoglobulin Fab Fragments / Q000097:blood / Q000235:genetics / Q000378:metabolism; D007128:Immunoglobulin Fragments / Q000097:blood / Q000235:genetics; D007074:Immunoglobulin G / Q000097:blood / Q000235:genetics / Q000378:metabolism; D007132:Immunoglobulin Isotypes / Q000097:blood / Q000235:genetics; D008657:Metabolic Clearance Rate; D016499:Radioimmunotherapy; D019275:Radiopharmaceuticals / Q000493:pharmacokinetics*
D000911:Antibodies, Monoclonal; D007140:Immunoglobulin Fab Fragments; D007128:Immunoglobulin Fragments; D007074:Immunoglobulin G; D007132:Immunoglobulin Isotypes; D019275:Radiopharmaceuticals