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 I-125-sc(Fv)(2)BMP in mice bearing LS-174T xenografts were comparable to these of the parent I-125-sc(Fv)(2). Complexing of scFvBMPs with streptavidin increased tumor targeting and gave exceptionally high tumor-to-blood values of 63 +/- 7 for I-125-sc(Fv)(2)BMP-streptavidin compared with 37 +/- 4 for sc(Fv)(2)BMP at 72 h after administration. High tumor and negligible normal tissue levels of these novel pretargeting constructs indicate a great potential for pretargeted radioimmunotherapy. (C) 2003 Elsevier Science Inc. All rights reserved.