MEDICINE / ORGAN TRANSPLANTS : Experimental Protein May Prevent Implant Rejections

Chicago scientists working with animals have reported an advance that, if effective in humans, promises to make organ transplants safer, cheaper and much more readily available. The researchers found that a genetically engineered protein protects transplanted organs against rejection without interfering with the immune system’s ability to combat infections.

Administered to mice for only the first two weeks after a transplant of human pancreatic tissues, the protein produced a lasting “tolerance” to the foreign tissue, the scientists said.

In contrast, drugs used to prevent organ rejection in humans must be given for the rest of the transplant recipient’s life. The drugs also interfere with the recipient’s ability to resist disease and can have severe side effects.

The new protein, described in today’s edition of the journal Science, could not only make human-to-human transplants more effective, but could also greatly improve the success of animal-to-human transplants, such as the recent use of a baboon liver in a Pittsburgh man.

The experimental drug, which will not be tested in humans for at least five years, would make a much larger number of organs available, easing the long waiting periods that exist for hearts and other key organs.

“This is a whole new way of treating transplantation,” said Dr. Ronald H. Schwartz, an immunologist at the National Institute of Allergy and Infectious Diseases in Bethesda, Md.

If the technique can be perfected in humans, said Dr. J. Richard Thistlethwaite, a transplant surgeon at the University of Chicago Medical Center and a co-author of the paper, “we will have solved the major problem facing organ transplantation today.”

Nearly 16,000 organ transplants will be performed in the United States this year, but because of shortages of organ donors, more than 26,000 people are on waiting lists for transplants. For some rarer organs, such as hearts, the wait can exceed three years.

The ability to use human organs that are not immunologically compatible with the recipient or to use organs from animals could sharply reduce or eliminate the wait.

The new protein, called CTLA4Ig, was developed by molecular biologist Peter S. Linsley and his colleagues at the Bristol-Myers Squibb Pharmaceutical Research Institute in Seattle. It is a modified form of a protein normally found in human immune cells.

The protein under study binds to a specific protein on the surface of the white blood cells that would normally reject transplanted tissues, thus tricking the immune system into not recognizing the tissue as foreign. After two weeks or so, the immune system in effect “loses interest” in the transplant but retains the ability to recognize infectious agents or tissue from a different donor.

The Chicago team headed by Dr. Jeffrey A. Bluestone, an immunologist, reported in the Science paper on the first 19 mice treated with the drug, but the group has since successfully treated several times that number, he said in a telephone interview.

Dr. Craig Thompson, an immunologist at the University of Michigan in Ann Arbor, has obtained similar successful results using the CTLA4Ig protein to transplant hearts from one species of rat to another.

Bluestone plans to conduct experiments on primates as soon as Bristol-Myers Squibb can produce enough CTLA4Ig for the experiment.

“That will be the major leap,” Bluestone said. “The things we see in small animal models aren’t always translated into humans. We’ll have to wait and see what happens in the primates before we even consider clinical studies” in humans.