Preclinical Studies and Optimization of Specific Tumor Delivery for 741F8 sFv, an Anti-c-erbB-2 Single-Chain Species

Abstract

AbstractSingle-chain Fv fragments (sFv) that bind tumor-associated antigens exhibit highly specific tumor targeting characteristics, based on studies of intravenous sFv administration to immunodeficient mice bearing human tumor xenografts. These features suggest that sFv may be used as targeting vehicles for diverse agents such as radionuclides, toxins, chemotherapeutic agents, or genes. However, the quantitative tumor retention of sFv molecules is lowered by their fast clearance and rapid dissociation from antigen. We have found that the retention of tumor-specific 74IF8 sFv in tumor is an antigen-specific event and not the result of extravascular pooling. We also have produced divalent 741F8 (sFv')2 species and have examined their pharmacokinetics and biodistribution properties in relevant tumor-bearing scid mice. Finally, we have employed a number of strategies to optimize the tumor-specific retention of radiolabeled sFv molecules; escalations in administered doses, repetitive intravenous bolus adminis...