Constructs of biotin mimetic peptide with CC49 single-chain Fv designed for tumor pretargeting.
Single-chain Fv constructs comprising a biotin mimetic peptide (BMP) and scFv of CC49 monoclonal antibody were produced to improve pretargeted radioimmunotherapy. BMP units that bind streptavidin were added to the carboxyl terminus of the CC49 V(H) region. An engineered scFvBMP monomer and a sc(Fv)(2)BMP dimer showed an excellent antigen recognition in vitro with a specific binding of 72+/-5 and 81+/-4%, respectively. Properties of 125I-sc(Fv)(2)BMP in mice bearing LS-174T xenografts were comparable to these of the parent 125I-sc(Fv)(2). Complexing of scFvBMPs with streptavidin increased tumor targeting and gave exceptionally high tumor-to-blood values of 63+/-7 for 125I-sc(Fv)(2)BMP-streptavidin compared with 37+/-4 for sc(Fv)(2)BMP at 72h after administration. High tumor and negligible normal tissue levels of these novel pretargeting constructs indicate a great potential for pretargeted radioimmunotherapy.
Department of Radiation Oncology, 981050 Nebraska Medical Center, University of Nebraska Medical Center, Omaha, NE 68198-1050, USA. gpavlink@unmc.edu
Gabriela
G
Pavlinkova
Surinder K
SK
Batra
David
D
Colcher
Barbara J M
BJ
Booth
Janina
J
Baranowska-Kortylewicz
D000818:Animals; D000912:Antibodies, Neoplasm / Q000276:immunology* / Q000378:metabolism; D000951:Antigens, Neoplasm / Q000276:immunology; D001710:Biotin / Q000737:chemistry*; D002851:Chromatography, High Pressure Liquid; D004591:Electrophoresis, Polyacrylamide Gel; D007128:Immunoglobulin Fragments / Q000276:immunology* / Q000378:metabolism; D007456:Iodine Isotopes; D051379:Mice; D018716:Molecular Mimicry; D009368:Neoplasm Transplantation; D009369:Neoplasms / Q000188:drug therapy* / Q000276:immunology*; D016499:Radioimmunotherapy / Q000379:methods*; D019809:Streptavidin / Q000008:administration & dosage / Q000494:pharmacology; D013379:Substrate Specificity; D013997:Time Factors; D014018:Tissue Distribution
D000912:Antibodies, Neoplasm; D000951:Antigens, Neoplasm; C091202:B72.3 antibody; D007128:Immunoglobulin Fragments; D007456:Iodine Isotopes; C055966:immunoglobulin Fv; D001710:Biotin; D019809:Streptavidin