An antibody that protects against radiation-induced lung fibrosis could improve the treatment of cancers that stem from radiation damage to the lungs, according to a study.
The research demonstrated that an antibody against connective tissue growth factor, or CTGF, prevented pulmonary fibrosis in up to 80 percent of irradiated mice. Those results have led to the antibody entering clinical trials for other fibrotic diseases.
The study, “Effects of CTGF Blockade on Attenuation and Reversal of Radiation-Induced Pulmonary Fibrosis,” was published in the Journal of the National Cancer Institute.
“We know that a whole number of growth factors and inflammation-promoting chemical messengers play a role in the development of fibrosis,” Peter Huber of the German Cancer Research Center, the senior author of the study, said in a press release. “But until now, agents targeting these molecules have not been effective enough to prevent pulmonary fibrosis or to improve its symptoms significantly. Much less was it possible to reverse fibrosis once it had developed.”
The research team has long searched for a compound that could prevent, and possibly even reverse, lung fibrosis.
They decided to test the antibody that targets CTGF, which is a fibrosis-promoting factor, in mice exposed to radiation. They measured CTGF levels at different points before and after radiation.
The antibody prevented fibrosis in 50% to 80% of the mice, depending on when it was administered. More importantly, it reversed fibrotic processes that had already begun.
When the antibody was administered 16 weeks after radiotherapy, it reversed half of the mice’s lung damage. The animals had better lung function and survived longer.
The antibody even protected mice from radiation doses that would normally have been lethal.
“The process of fibrotic tissue transformation following radiation therapy is very similar in mice and in men,” said Sebastian Bickelhaupt, the study’s first author. “This suggests that our results are also relevant for humans affected by fibrosis.”
That idea is now being tested in clinical trials of the antibody.
“The protection from fibrosis that we have been able to achieve using the antibody against CTGF in mice was impressive,” Huber said. “We, therefore, think that it is promising to test the antibody also in humans who have to undergo radiotherapy. Additionally, patients with other types of fibrotic disease that are not related to radiation might also benefit from a blockade of CTGF.”
“And maybe even the chances of curing the cancer will improve: If we reduce radiation-induced side effects, we can increase the radiation dose in the tumor,” he added.