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.
Publication types
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Comparative Study
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Research Support, U.S. Gov't, Non-P.H.S.
MeSH terms
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Animals
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Antibodies, Monoclonal / genetics
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Antibodies, Monoclonal / pharmacokinetics*
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Antibodies, Neoplasm / genetics
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Antibodies, Neoplasm / metabolism*
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Cell Line, Tumor
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Colonic Neoplasms / metabolism*
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Colonic Neoplasms / radiotherapy
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Female
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Immunoglobulin Fragments / genetics
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Immunoglobulin Fragments / metabolism*
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Iodine Radioisotopes / pharmacokinetics*
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Iodine Radioisotopes / therapeutic use
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Metabolic Clearance Rate
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Mice
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Mice, Nude
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Organ Specificity
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Protein Engineering / methods*
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Radioimmunotherapy / methods
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Radiopharmaceuticals / pharmacokinetics
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Radiopharmaceuticals / therapeutic use
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Tissue Distribution
Substances
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Antibodies, Monoclonal
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Antibodies, Neoplasm
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B72.3 antibody
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Immunoglobulin Fragments
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Iodine Radioisotopes
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Radiopharmaceuticals