Kidney Rejection Prevented in Monkeys

A new drug taken for just a few months has prevented monkeys from rejecting transplanted kidneys. The drug, described in the June Nature Medicine, also lacks the side effects of immunosuppressive drugs, such as heightened vulnerability to infection. Human trials are just getting under way, but the primate results are "really, truly amazing," says transplant immunologist Norma Kenyon of the University of Miami in Florida.

The drug is an antibody that binds to a protein called CD154, one of the signals that the immune system needs to launch an attack against a microbial invader or transplanted tissue. The antibody thwarts the attack by binding to CD154 and preventing it from binding to its receptor.

The strategy has so far surpassed expectations. Immunologist Allan Kirk and endocrinologist David Harlan of the Naval Medical Research Center in Bethesda, Maryland, and their colleagues gave nine monkeys weekly doses of the antibody for the first month after their transplant, and monthly doses for 5 months afterwards. All treatment was then stopped. More than a year later, eight of the nine are alive and well. The one death was due to complications during a routine blood draw; an autopsy revealed that the monkey had normally functioning kidneys when it died. Control monkeys that received standard immunotherapy died within 9 weeks.

No one is sure why the monkeys' immune systems accept the foreign tissue long after the drug is stopped. Some scientists suspect that immune cells activated by the foreign organ but lacking the CD154 signal die soon after a transplant, although it's not clear why new generations of immune cells wouldn't recognize and attack the tissue. Others suspect that the "stalled" immune cells may somehow be protective.

The scientists caution that it's too soon to know if the acceptance is permanent--activated immune cells that the scientists have found in the kidneys could still lead to eventual rejection. Even so, says transplant immunologist Christian Larsen of Emory University, "it is spectacular to have a monkey off of immunosuppression, with good graft function, for more than a year."