Immune Hybrid Illustration

Making An Immune-System Hybrid

The technique might free transplant recipients from lifelong drug regimen

Amy Adams
Illustration Jeffrey Fisher

The science of organ transplantation has come a long way. Once concerned only with getting the transplanted organ to function in the recipient, doctors now seek to increase the long-term survival of the transplanted organ while maintaining the recipient's quality of life. "Transplantation is a life-saving procedure, but the price is the lifelong use of immune-suppressing drugs," says Samuel Strober, MD, professor of immunology and rheumatology. These powerful drugs prevent rejection of the organ but leave transplant recipients open to infection and increase the risk of heart disease or cancer.

Now researchers at Stanford, led by Strober, are working on a way to reduce or even eliminate transplant recipients' dependence on drugs. In a study published in May in the journal Transplantation, the doctors, hoping to avoid the rejection of a new organ as foreign, created a hybrid donor-recipient immune system in four kidney transplant patients.

Organ rejection after transplantation occurs because the immune system scans for foreign cells. If the immune system in the transplant recipient weren't heavily suppressed, it would attack cells in the transplanted organ, leading to rejection.

This new approach to kidney transplantation began normally, with surgery followed by immune-suppressing drugs, which were needed to prevent organ rejection while the team completed the next step.

After the transplant, the kidney recipient received multiple small doses of radiation targeted to the immune system along with a drug to reduce the number of cells capable of an immune attack. The team then injected blood stem cells from the kidney donor into the recipient. The stem cells made their way to the recipient's bone marrow where they produced new blood and immune cells that mixed with those of the recipient.

A sample of the patient's cell mixture did not attack donor cells in the laboratory, which indicated that the new hybrid immune system should not mount an attack against the transplanted organ. At that time, the team slowly weaned the patient away from the immune-suppressive drugs.

Two patients who stopped taking drugs experienced mild rejection episodes. They are back on low doses of medication. A third patient is still tapering off drugs, while the fourth suffered a rejection episode before tapering and must remain on medication. Strober hopes to prevent rejection in future patients by injecting more donor stem cells. FDA approval of a 10-patient study is pending.

Co-author Maria Millan, MD, transplant surgeon at Stanford Hospital and assistant professor of surgery, said this study represents the direction in which transplantation will move in the future. "We've topped out on what we can do with drugs," Millan says.

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