SOURCE: Sidney Kimmel Cancer Center

March 07, 2007 14:35 ET

Selective, Speedy Shuttle Service in Cells Lining Blood Vessels of Lungs: A NEW GATEWAY for Pumping THERAPEUTIC and Imaging Agents Rapidly Into Tissue at LOWER DOSAGES

SAN DIEGO, CA -- (MARKET WIRE) -- March 7, 2007 -- For the first time in a live animal, scientists have been able to see how the cells that line the inside of blood vessels can capture specific targeted molecules from the blood stream and move them rapidly into the tissue.

In the current Nature Biotechnology [], the scientists, who are based at the Sidney Kimmel Cancer Center (SKCC) in San Diego [], report that the caveolae, little balloon-like structures on the cells' surface, were so efficient and fast at pumping and concentrating the targeted molecules, which are monoclonal antibodies, that an unusually large quantity of the antibodies succeeded in reaching the inside of the lung tissue.

Viewing this process in real time, Jan Schnitzer, M.D., and his team at SKCC saw the potential for harnessing the monoclonal antibodies tailored to interact only with caveolae, for basic research as well as for the medical care of people with a variety of lung diseases including cystic fibrosis, pulmonary fibrosis, and tuberculosis and other respiratory infections.

"This is an important advancement because the desired site of action of most therapies is usually a cell located deep inside the tissue," explained Dr. Schnitzer. "In the past, the endothelial cells lining the blood vessels have been an enemy to most therapies by preventing access inside the tissue. Both nanomedicine and gene therapy have suffered because of poor access and thus may benefit greatly from the caveolae pumping pathway. But now the endothelial cells can become a friend via this gateway for the monoclonal antibodies to reach the inside of lung tissue."

Dr. Schnitzer and his colleagues used proteomics analysis to identify specific targets in lung caveolae and then custom designed the monoclonal antibodies so that they would latch only onto proteins unique to the cells' caveolae.

Monoclonal antibodies targeted to caveolae, Dr. Schnitzer explained, potentially can be used to deliver powerful drugs to lung tissue at the low dosage levels that become more effective, because they concentrate the drug inside the tissue relevant in combating the disease. Because monoclonal antibodies can be designed to interact with proteins unique to the caveolae, and not common in other body organs, the risk that medications transported by the lab-produced antibodies would reach and thereby harm healthy tissue may become negligible, said Dr. Schnitzer.

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    Jan Percival