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Ralph C. Corley Distinguished Professor, Department of Chemistry, Purdue University

"Ligand-targeted delivery of therapeutic and imaging agents to cancer tissues and sites of inflammation"

Prof. Philip Low

Monday February 07, 2011

4:00pm PHYS 203

Unless otherwise noted, seminars are held on Tuesdays at 4:00 p.m. in Physics Room 203. Coffee and doughnuts served at 3:45pm.

http://www.chem.purdue.edu/people/faculty/faculty.asp?itemID=44

We have developed methods to target drugs specifically to pathologic cells, thereby avoiding collateral toxicity to healthy cells. To achieve this specificity, we have searched for ligands that bind selectively to diseased cells and have linked these ligands to therapeutic agents to promote their selective uptake by the pathologic cells. In the case of cancer, we have exploited the up-regulation of the folate receptor on malignant cells to target the following pharmaceuticals to cancer tissue in vivo: i) protein toxins, ii) chemotherapeutic agents, iii) gene therapy vectors, iv) oligonucleotides, v) radioimaging agents, vi) MRI contrast agents, vii) liposomes with entrapped drugs, viii) radiotherapeutic agents, ix) immunotherapeutic agents, and x) enzyme constructs for prodrug therapy. Current clinical trials of six folate-linked drugs demonstrate that the folate receptor-targeting strategy holds great promise for increasing drug potency while reducing unwanted toxicities. Data from some of these trials will be presented. Recently, we have also developed a ligand that selectively targets attached drugs to prostate cancer cells with ~10 nM affinity. Imaging and therapeutic studies suggest that the new prostate cancer-specific ligand can not only improve diagnosis of the disease, but also enhance treatment of the cancer with little or no toxicity to normal cells. Other ligands that target pancreatic, stomach and esophageal cancers are also undergoing analysis. Outside of the cancer field, we are also developing drug targeting strategies for the imaging and therapy of rheumatoid arthritis, Crohn’s disease, atherosclerosis, lupus, osteoarthritis, diabetes, and multiple sclerosis. Results from preclinical and clinical studies with these latter targeted drugs will also be described. Finally, a summary of the advantages and potential pitfalls associated with ligand-targeted delivery will be described.