Construction, Binding Properties, Metabolism, and Tumor Targeting of a Single-Chain Fv Derived from the Pancarcinoma Monoclonal Antibody CC49

摘要: CC49 is a "second generation" monoclonal antibody to B72.3, which reacts with the pancarcinoma antigen TAG-72. has been shown efficiently target human colon carcinoma xenografts and currently being evaluated in both diagnostic therapeutic clinical trials. We describe here construction characterization of recombinant single-chain Fv (sFv) CC49. The sFv was be Mr 27,000 homogeneous entity could radiolabeled 125I or 131I. Comparative direct binding studies competition radioimmunoassays using intact IgG, F(ab')2, Fab', revealed that monomeric Fab' had relative affinities 8-fold lower than dimeric F(ab')2 IgG. Nonetheless, 131I-labeled bind biopsies TAG-72-expressing tumors. Metabolism mice, sFv, demonstrated an extremely rapid plasma whole body clearance for sFv. pharmacokinetic rhesus monkeys also showed very (T1/2 alpha 3.9 min T1/2 beta 4.2 h). Tumor targeting all four Ig forms, LS-174T xenograft model, much percentage injected dose/g tumor as compared However, tumor:normal tissue ratios (radiolocalization indices) were comparable greater those other forms. High kidney uptake 125I-labeled not seen 125I-sFv. Gamma scanning 131I-CC49 localize may thus have utility perhaps applications range carcinomas.