CAR T-cell therapy has enabled two patients who had been waiting for years for a kidney transplantation to find a match. Published today in the New England Journal of Medicine, preliminary results from a Phase I clinical trial show that CAR T therapy can significantly increase the chances of a match for people whose immune system would otherwise reject over 99% of kidneys available for transplant.
“This is the first demonstration that CAR T cells can be used not only to treat cancer, but also to help patients who previously had no opportunity to receive a compatible donor kidney,” said Ali Naji, MD, PhD, professor of surgery at the University of Pennsylvania and principal investigator of the study. “For patients who have spent years on the kidney transplant waiting list, this approach could be transformative.”
More than 91,000 people in the U.S. are currently waiting for a kidney transplant. Physicians assess each patient’s likelihood of finding a compatible donor using the calculated panel reactive antibody (cPRA) score, which measures how broadly the immune system is primed to attack foreign tissues. For instance, a cPRA score of 90% means the patient is expected to reject 90% of kidneys available for transplant, leaving only a small pool of potential matches available to them.
The ongoing CTOT-46 clinical trial is recruiting kidney transplant candidates with a cPRA score of 99.5% or higher who have been waiting for a kidney transplant for at least one year. Although the study will continue until up to 20 highly sensitized candidates have been recruited, preliminary results from the first two patients enrolled show promise for this innovative approach.
Both participants were treated with a dual CAR T therapy designed to remove the immune cells responsible for making antibodies that lead to organ rejection after a kidney transplant. The CAR T cells are engineered to target the CD19 and BCMA proteins, leading to the depletion of memory B cells and antibody-producing plasma cells, respectively. This strategy significantly reduced the levels of circulating antibodies produced by these cells, enabling both patients to receive kidneys from donors that would have previously been incompatible.
One of the patients had been diagnosed with focal glomerulosclerosis at age 14, leading to kidney failure at a young age. His cPRA score had reached nearly 100% after his immune system rejected a second kidney transplant, making a third transplantation next to impossible. After years of waiting for an extremely unlikely match, the CAR T cells lowered his antibody levels enough to find a match within months.
Importantly, the depletion of immune cells was temporary, and the population of B cells and plasma cells returned to normal levels over time. Neither of the patients has shown signs of organ rejection or antibody rebound months after transplantation. Additionally, no cases of severe cytokine release syndrome or neurotoxicity were reported—two common complications of CAR T-cell therapy.
“In this early trial, the CAR T-cell treatment was tolerated well, with no severe side effects, and the immune system began to recover as expected,” said Robert Montgomery, MD, PhD, chair of the department of surgery at NYU Grossman School of Medicine and director of the NYU Langone Transplant Institute. “This early success reflects what cell therapy can do for transplant medicine and opens up new options for patients that could save thousands more lives every year.”
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