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 VH region. An engineered scFvBMP monomer and a sc(Fv)2BMP dimer showed an excellent antigen recognition in vitro with a specific binding of 72±5 and 81±4%, respectively. Properties of 125I-sc(Fv)2BMP 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)2BMP-streptavidin compared with 37±4 for sc(Fv)2BMP at 72h after administration. High tumor and negligible normal tissue levels of these novel pretargeting constructs indicate a great potential for pretargeted radioimmunotherapy.
- Biotin mimetic peptide
- Pretargeting radiotherapy
- Single-chain antibody fragments
ASJC Scopus subject areas
- Cellular and Molecular Neuroscience