Event
Bioengineering Seminar Series: Philip S. Low
Friday, September 9, 2011
11:00 a.m.
Room 1200 Jeong H. Kim Engineering Bldg.
Professor Silvia Muro
muro@umd.edu
Ligand-Targeted Therapeutic and Imaging Agents for Cancer and Inflammatory Diseases
Philip S. Low
Ralph C. Corley Distinguished Professor
Department of Chemistry
Purdue University
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 the design, development and human testing of some of these drugs 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, Crohns 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.
About the Speaker:
Dr. Low is the Ralph C. Corley Distinguished Professor of Chemistry at Purdue University and the founder of Endocyte Inc. Dr. Low has spent ~20 years in drug targeting research and has published over 300 scientific articles and received ~35 US patents/patent pending. He has served on National Institutes of Health Study Sections and has received an NIH MERIT Award. Dr. Low has also received both of Purdue University's awards for outstanding research and has guided the discovery and development of 7 drugs that are currently in human clinical trials. Dr. Low received his Ph.D. in Biochemistry from University of California, San Diego in 1975.
