|Vol. 24, No. 3||February 15, 2002|
Researchers Identify "ZIP Codes" in the Human
Blood Vessel System
by JULIE A. PENNE
The University of Texas
M.D. Anderson Cancer Center
Researchers at The University of Texas M.D. Anderson Cancer Center are one step closer to creating the first molecular map of the human blood vessel system, potentially widening the opportunity for new targets for therapeutic agents.
A study, published in the February issue of Nature Medicine, describes a method for identifying "vascular ZIP codes," specific and unique addresses in the human body to which drugs may someday more efficiently and effectively be delivered. Drs. Wadih Arap and Renata Pasqualini, both associate professors in M.D. Anderson’s departments of genitourinary medical oncology and cancer biology, are the senior authors of the report.
"The identification of human vascular ZIP codes brings medicine’s ultimate goal of targeted therapies that much closer to reality," said Dr. Pasqualini. "Vascular targeting may improve the effectiveness of a therapy by zeroing it in on the tumor site while sparing the healthy parts of the body. However, the molecular diversity of blood vessels has just been uncovered, and there is much more work to be done."
By administering a collection of more than a billion peptide sequences displayed in microscopic particles called phage, the M.D. Anderson researchers found that the peptides homed preferentially to specific areas of the body. This large-scale screening shows that the tissue distribution of circulating peptides is nonrandom and that certain peptides direct and bind to different organs.
The researchers report that the peptides bind to receptors present in the blood vessels and organs. While traveling through the body, peptides may stimulate the behavior of ligands (peptide-binding proteins) and respond like a lock-and-key system as they interact with receptors in the blood vessels or organs.
Specific peptides bind to a specific organ or blood vessel, Dr. Pasqualini said.
"This is the first time such an approach has been used in humans," said Dr. Arap. "This is akin to doing a ‘molecular mass mailing’ to all addresses in the body. The peptides travel until they find a target and bind to it. The technology we are using allows them to be recovered and identified. Because we know the characteristics of the peptides and where they attach, we can better understand the molecular makeup of the vascular system and then tailor therapies that will home to disease sites."
The injection of the peptide collection was the first step in the study, followed by biopsies done from various tissues to determine where and how the peptides homed.
The biopsies were taken from a patient with advanced cancer, who was declared brain dead by a physician not associated with the study. The patient had developed multiple complications as a result of his disease and was critically dependent on a ventilator in the intensive care unit. When the family decided to remove the ventilator, they told intensive care staff that the patient had wanted to donate his organs upon his death. Since the patient was not eligible for organ transplant donation because of the extent of disease, the possibility of participating in this study was offered.
The bedside procedure was performed within a one-hour time frame, the researchers reported.
"From transplant literature, we know that donating a loved one’s body to help others live can help families bring meaning to their loss because they feel like they are doing something positive," said Dr. Rebecca Pentz, former clinical ethicist at M.D. Anderson and now an ethics consultant in Atlanta. "This patient’s family told us he wanted to give something back to M.D. Anderson. This research was a way to meet the patient’s goals, even after his death."
The study was funded by grants from the National Cancer Institute and the Department of Defense, and by awards from Cap CURE, the Gilson-Longenbaugh Foundation and the Susan G. Komen Foundation.
M.D. Anderson Cancer Center has licensed the technology to NTTX Biotechnology Inc., a biotechnology company that will develop the technology and information into clinical applications.
©2006 Texas Medical Center