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Antibody-Based Drug Carriers for Targeted Prostate Cancer Chemotherapy
Final rept. 31 Oct 2004-30 Apr 2006
TEXAS UNIV HEALTH SCIENCE CENTER AT HOUSTON
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The goal of this project was to create a universal, antibody-based drug delivery system for targeted delivery of small chemotherapeutic drugs to the site of prostate cancer. The authors wanted to explore the ability of the antibodies to reversibly hold small organic molecules haptens or antigens via non-covalent interactions with six flexible polypeptide loops CDRs. Binding of this class of molecules, including chemotherapeutic drugs, usually does not require the participation of all six CDR loops. The authors propose to use these underutilized CDR loops to target the antibody carrier to the cancer site by replacing it with loop-shaped peptides specific to the cancer site. The first aim of the project was to modify the existing human phage display library by introducing a prostate-homing peptide into the 3rd CDR loop of the light chain. The modified library was used to select a group of Fvs specific for a model chemotherapeutic drug, doxorubicin DOX. Selected Fvs were characterized for their affinity to DOX using spectrofluorometric measurements. The second aim of the project was to evaluate the potential of selected Fvs to deliver DOX to the prostate tissue in mice. Panning of the library with doxorubicin conjugated to BSA yielded a panel of monoclonal doxorubicin specific Fvs that could be used as prostate tissue-specific carriers of this drug with increased tissue selectivity and reduced toxicity.
APPROVED FOR PUBLIC RELEASE