Novel targeting of biotinylated compounds to local tissues with avidin-lipoprotein receptor fusion protein.
Extract: Targeting of cytotoxic drugs, radionuclides or imaging agents to specific cells or tissues is of great interest for the development of new therapeutic strategies and diagnostic approaches. Targeting should significantly increase efficacy in the desired tissues and reduce side effects elsewhere in the body. Previously, avidin or streptavidin have been used in multistep pretargeting applications either as a fusion protein with a cancer-targeting antibody or as a linker between biotinylated cancer-targeting antibodies and biotinylated radionuclides. However, these three step strategies (i.e., cancer tissue-specific biotinylated antibody; avidin or streptavidin; biotinylated drug) are complicated to use, involve the systemic injection into patients of three different compounds and sometimes only marginally improve the therapeutic window. Also, cancer tissue-specific monoclonal antibodies have been difficult to develop and each type of tumor would require the development of different monoclonal antibodies.
Ylä-Herttuala
Seppo
S
A.I. Virtanen Institute, University of Kuopio, P.O. Box 1627, FIN-70211 Kuopio, Finland.