Human tumor-specific phage nanoparticles
S.D. Ireland Professor of Surgery
The University of Vermont
Dr. Krag received his medical degree from Loyola Stritch School of Medicine, Chicago, and did his residency in general surgery at the University of California, Davis. He held a fellowship in surgical oncology research at the John Wayne Cancer Center, Los Angeles.
Dr. Krag’s laboratory is using the methodology of phage-displayed random peptide libraries (RPLs) to develop short peptide ligands for anticancer therapy. The goal is to develop peptide ligands with high affinity to appropriate cancer targets. Synthetic DNA with random sequences are inserted into phage genome such that peptide product is expressed on the outer protein coat of the phage particle. Each phage expresses a unique peptide and millions of different peptides are present (on millions of different phage) in a single "library." The library is exposed to a target material and screened for those peptides that bind to the target. Only those unique peptides that have good binding affinity stick. An alternative strategy to screening libraries against purified targets is to administer the RPL intravenously to a cancer patient, surgically harvest a small tumor specimen, and identify phage that bind to the tumor. A phase I study exploring this latter strategy is open for accrual.
Dr. Krag’s laboratory is also evaluating the optimal methods for detecting rare cancer cells in the circulating blood of cancer patients. Fifty to 75 percent of cancer cells that have been added to blood can be reliably detected. Determining the prevalence of cancer cells in the blood of breast or colon cancer patients is now in progress. Combining the methods of rare event cancer cell detection with phage-display panning methods to determine the feasibility of panning for peptide ligands on rare cancer cells detected in the blood or bone marrow is also ongoing.
Since 1992, Dr. Krag has been continuously involved in the development of radio-guided surgical resection of sentinel nodes in breast cancer patients. The current research, in partnership with the National Surgical Breast and Bowel Project (NSABP), is conducting a Phase III randomized study of sentinel node dissection with or without conventional axillary dissection in women with clinically node negative breast cancer. Dr. Krag is principal investigator of this sentinel node study.
Speaking in the special symposium on Phage Nanobiotechnology.