PITTSBURGH — As Barbara Bowser was preparing for a liver transplant in 2018, doctors at the University of Pittsburgh asked her if she’d be willing to participate in a study.

She said yes, happy to repay the good fortune of receiving a liver and help science in the process.

“We were just looking at research in the future,” she said. “We never ever thought it would work.”

Bowser, of Punxsutawney, hasn’t taken an antirejection drug in more than six years. She is one of three liver transplant patients in the Pitt study who have been able to discontinue taking all antirejection medications for at least three years since their transplants. In the study, Pitt researchers injected the liver recipients with cells altered from the blood of their liver donors to instruct the recipient’s immune system that the new liver was not a threat.

The study, published Friday in the journal Nature Communications, is the first to test that approach on human patients.

“We have been able to get a proportion of these patients off all antirejection therapy quite early post-transplant,” said senior author Angus Thomson, distinguished professor of surgery and immunology at Pitt, “and they have remained off antirejection therapy for several years.”

Managing rejection has been a persistent issue in organ transplant since the days of Dr. Thomas E. Starzl at Pitt. The body has a natural tendency to fight a donated organ as a foreign body, and the solution has always been a lifelong course of antirejection drugs. Those drugs have side effects, however, in suppressing the immune system and putting patients at risk for infections, kidney damage and some cancers.

“The goal that we and the entire transplant community would like to achieve is something called tolerance,” said first author Abhinav Humar, clinical director of the Starzl Transplant Institute and chief of the division of transplantation at UPMC, “the ability to have the transplant without the need for long-term antirejection medications.”

It’s a problem that Thomson first started investigating in a laboratory at Pitt in 1995, when he hypothesized that a type of immune cell, called a regulatory dendritic cell, could play a role in organ rejection.

After decades in the lab, he and other Pitt researchers were ready to test the hypothesis in humans in 2017, with funding from UPMC Enterprises.

“It may seem like an extraordinarily long time,” said Thomson, “but it’s not exceptional in developing a new scientific approach from the basic laboratory level to a first-in-human clinical trial.”

A few weeks before a living donor transplant, they took filtered white blood cells from the donor and used them to prepare the regulatory dendritic cells. Those cells were programmed with instructions to recognize the liver from the donor as friendly cells, rather than an invading foreign body.

A week before transplant, they injected the cells into the recipient and then proceeded with the transplant and antirejection drugs as normal. About a year after transplantation, they tested the patients’ immune response to evaluate whether they could stop the antirejection drugs without risking organ rejection.

Of the 13 patients in the study, they felt comfortable removing the drugs in eight patients, with four ultimately withdrawing from the drugs completely and three doing so for a period of at least three years.

While the study is small and primarily exploratory, the results are encouraging in demonstrating that this therapy is both safe and effective, said Humar.

The liver is an ideal organ to study rejection tolerance, he said, because it tends to be more forgiving of rejection than other organs, such as the kidneys. “The penalty paid for a rejection episode is a lot less,” he said. “And also when rejection happens, it is easier to treat.”

This therapy is also designed for organs from living donor transplants, since the procedure begins weeks before the transplant itself.

The Pitt researchers have applied for funding from the National Institutes of Health for a study to examine the same therapy in a larger population, with a randomized control group. They also would examine giving the dendritic cells to the recipient after transplantation rather than before, which would allow the therapy to be used in transplants with deceased donors.

If funded, it will likely be the next in years of more research studies.

“We know that tolerance is not something that’s going to be easy to achieve,” said Humar. “We’ve been trying it for the better part of 50-plus years and haven’t solved it. You’re trying to fool Mother Nature, which has taken millions of years to develop. … Like so many other things in medicine, the progress is going to need to be incremental.”

For Bowser, however, progress came fast enough for her. For the year that she took the antirejection medicines after the transplant, she caught more illnesses, felt like she couldn’t focus well and experienced hair loss. She is grateful not just to have found a living donor on Facebook when she needed a transplant after liver cancer, but also to be able to live without immunosuppressants.

Near her computer, she keeps a quote written down that her donor posted on Facebook: “You have never really lived until you have done something for someone who can never repay you.”

“I kind of try to live by that,” she said. “You’ve got it so good and you are so blessed. That’s the reason we decided to do the study. We figured it would be something to build on, and maybe the next time, it would be successful.”

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