title: The in vivo characteristics of genetically engineered divalent and tetravalent single-chain antibody constructs.
abstract: Engineered multivalent single-chain Fv (scFv) constructs have been demonstrated to exhibit rapid blood clearance and better tumor penetration. To understand the short plasma half-life of multivalent single-chain antibody fragments, the pharmacokinetic properties of covalent dimeric scFv [sc(Fv)2], noncovalent tetrameric scFv {[sc(Fv)2]2} and IgG of MAb CC49 were examined. The scFvs displayed an ability to form higher molecular aggregates in vivo. A specific proteolytic cleavage of the linker sequence of the covalent dimeric or a deterioration of the noncovalent association of the dimeric scFv into tetravalent scFv constructs was not observed. In conclusion, sc(Fv)2 and [sc(Fv)2]2 are stable in vivo and have significant potential for diagnostic and therapeutic applications.
authors.affiliation: Department of Biochemistry and Molecular Biology, Eppley Institute for Research in Cancer and Allied Diseases, University of Nebraska Medical Center, Omaha, NE 68198, USA.
authors.forename: Uwe A
authors.initials: UA
authors.lastname: Wittel
authors.forename: Maneesh
authors.initials: M
authors.lastname: Jain
authors.forename: Apollina
authors.initials: A
authors.lastname: Goel
authors.forename: Subhash C
authors.initials: SC
authors.lastname: Chauhan
authors.forename: David
authors.initials: D
authors.lastname: Colcher
authors.forename: Surinder K
authors.initials: SK
authors.lastname: Batra
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000235:genetics / Q000493:pharmacokinetics*; D000912:Antibodies, Neoplasm / Q000235:genetics / Q000378:metabolism*; D045744:Cell Line, Tumor; D003110:Colonic Neoplasms / Q000378:metabolism* / Q000532:radiotherapy; D005260:Female; D007128:Immunoglobulin Fragments / Q000235:genetics / Q000378:metabolism*; D007457:Iodine Radioisotopes / Q000493:pharmacokinetics* / Q000627:therapeutic use; D008657:Metabolic Clearance Rate; D051379:Mice; D008819:Mice, Nude; D009928:Organ Specificity; D015202:Protein Engineering / Q000379:methods*; D016499:Radioimmunotherapy / Q000379:methods; D019275:Radiopharmaceuticals / Q000493:pharmacokinetics / Q000627:therapeutic use; D014018:Tissue Distribution
chemical_list: D000911:Antibodies, Monoclonal; D000912:Antibodies, Neoplasm; C091202:B72.3 antibody; D007128:Immunoglobulin Fragments; D007457:Iodine Radioisotopes; D019275:Radiopharmaceuticals