A combination of radiation therapy and bavituximab, a monoclonal antibody that helps destroy blood vessels nourishing malignant tumours, is more effective in treating lung cancer than either approach alone, say researchers at UT Southwestern Medical Center.
The researchers based their results on the findings of a study in which human lung-cancer cells were implanted in mice.
AdvertisementDr. Philip Thorpe, professor of pharmacology, says that radiation generates a chemical reaction in the membranes of endothelial cells, which line the blood vessels that feed tumours. The reaction causes membrane components called anionic phospholipids to flip inside out, exposing them, he says.
"The flipping is likely due to stress conditions present in the tumor micro-environment, and radiation increases the number of exposed phospholipids," said Dr. Thorpe.
After inducing more flipping with radiation, the researchers administer bavituximab, which homes in on tumour vessels by selectively binding to the inside out phospholipids. The binding signals white blood cells from the immune system to attack, and destroy the vessels feeding the tumour.
During the study published in Clinical Cancer Research, the researchers found that radiation increased the percentage of phospholipids that flip inside out from 4 per cent to 26 per cent.
It was also found that treating the mice with bavituximab and radiation therapy together reduced tumour growth by 80 per cent, and was more effective than administering either treatment by itself.
"About 30 per cent of all lung-cancer patients receive radiation and, in this animal model of lung cancer, we found that this monoclonal antibody improves the efficacy of radiation therapy without the toxicity seen in other chemotherapeutic drugs. It's a win-win," said Dr. Thorpe.
Bavituximab, which was created in Dr. Thorpe's lab, is currently being tested in clinical trials in the U.S. and India for its effectiveness against solid-tumour cancers.
Vascular targeting agents such as bavituximab kill tumours without causing damage to surrounding healthy tissue. They cause fewer side effects than conventional cancer drugs that kill rapidly dividing normal cells along with the cancer cells.
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