A new method of identifying targets for the delivery of therapeutics to specific parts of the body has been discovered by researchers at the Sidney Kimmel Cancer Center (News) in San Diego. The details of the immunotargeting research are being published Jan. 10 in the Proceedings of the National Academy of Sciences.

Under the leadership of Scientific Director Jan Schnitzer, M.D., SKCC researchers discovered a method for more effectively identifying agents that target protein molecules in blood vessels.

"These new targeting agents can be used for selective diagnostic and prognostic imaging of normal and diseased tissues, including cancer and damaged lung or heart tissue, as well as for delivering drugs," Dr. Schnitzer explained.

Their findings are described in an article titled "Screening phage display libraries for organ-specific vascular immunotargeting in vivo." The article is now published online at the PNAS Web site: www.pnas.org.

"This new technology overcomes many of the problems and barriers researchers have encountered in the past," Dr. Schnitzer added.

Protein targets in tissue blood vessels can now be identified in vivo; that is, in living tissue. This is a critical distinction, because targets were previously identified ex vivo; that is, in cells grown in a cell culture.

But the problem with ex vivo analysis, the researchers found, is many proteins cannot be detected. For example, they found that 40 percent of endothelial cell surface proteins expressed in rat lungs in vivo are not detected ex vivo.

In addition, the SKCC researchers discovered a new technology for generating antibody-like molecules that target the blood vessels of a single tissue of the body.

"Our experiments show not only that we can find such targets, but that these targets to blood vessels work," Dr. Schnitzer said. "The newly discovered antibodies go to one organ of the body within minutes of injection."

The potential benefit for patients is that these discoveries may allow directed delivery of many therapeutics ­ including biologics, pharmaceuticals, gene vectors and nanomedicines ­ to specific tissue, such as cancer tumors, without endangering normal tissue.

"This lab is continuing this work to expand its application to the treatment of cancer and other diseases," Dr. Schnitzer said.

This research was supported by grants from the National Cancer Institute and the National Heart Lung and Blood Institute at the National Institutes of Health. This includes R01 grants on targeting endothelium in normal organs and cancer, a Program Project grant on targeting blood vessels, and a recent Nanotechnology Development Award to find new targets and probes to deliver nanoparticles and nanomedicines to specific tissues including solid tumors.

Also participating in this research are: Philippe Valadon (the first author of this publication), Jeff D. Garnett, Jacqueline E. Testa, Marc Bauerle and Phil Oh.