Copying a cancer trick prevents organ transplant rejection in rats
Cancer is a crafty foe, employing an array of tricky techniques to hide from the immune system while it grows. But now, scientists have managed to copy one of those strategies and use it for good, making new microparticles that permanently prevent transplanted tissue or even whole limbs from being rejected by the immune system.
Transplanted organs, tissue or limbs can be life-saving, but they come with a pretty big risk. The immune system can recognize that the new cells are foreign and reject them, causing serious health problems. The main treatment to prevent rejection is to suppress the immune system with drugs, but of course that can make patients more vulnerable to other illness and disease.
Surprisingly, cancer might hold the key to a more effective treatment. Tumors have an insidious ability to evade detection by the immune system, by secreting a protein called CCL22. This summons regulatory T cells (Tregs), which tag the body’s own cells as “self” so they’re ignored by immune cells. Once the tumor tricks the Tregs into tagging the cancer cells as safe, the disease can grow and spread.
For the new study, researchers at the University of Pittsburgh investigated how that cancer mechanism could help prevent transplant rejection. They developed synthetic particles that can emit CCL22 in the transplanted tissue, allowing it to avoid attack by the immune system.
"It's like hacking into the immune system borrowing a strategy used by one of humanity's worst enemies to trick the body into accepting a transplant," says Steven Little, senior author of the study. "And we do it synthetically."
The team tested the technique in rats, and found that just two injections of the treatment was enough to train their immune systems to accept the new graft. The benefit appeared to be permanent, lasting for the whole 200-plus-day period that they were monitored. And it wasn’t just a small tissue transplant either: entire hind legs were replaced in these rats.
While it’s still a long way off from human use, the researchers say that their method is a promising one. Being synthetic, it should be easier to scale up, they say. Similar studies are using banks of stem cells that can be genetically matched to a patient, new drugs that boost enzymes known to produce Tregs, and nanoparticles that suppress proteins that alert the immune cells to the transplant.
The new research was published in the journal Science Advances.