An immune tolerance treatment that has been 30 years in the making has shown promise in a small study where from 12 kidney transplant patients 8 were successfully weaned off their daily immunosuppressive drugs. As well as freeing patients from lifelong use of drugs, such a protocol could reduce long term side effects and bring substantial health-care savings.

Researchers from Stanford University School of Medicine reported their progress on what they describe as a proof-of-concept study, in a letter to the editor published in the New England Journal of Medicine on Thursday.

Kidney transplant patients have to take around 30 pills a day, mostly immunosuppressive drugs to stop their immune system rejecting the graft. While this does prolong life, for instance a patient with a well matched kidney from a live donor can expect to live another 25 or 30 years, it is expensive and there are long term cumulative side effects, including a higher risk of heart disease, infection, cancer and diabetes, write the researchers.

The man behind the new protocol is Dr Samuel Strober, an immunologist and professor of medicine at Stanford. He said in a statement:

“While they help ward off rejection of the new organ by the patient’s own immune system, these drugs carry their own risk of side effects, such as high blood pressure, diabetes and cancer.”

The drugs are also somewhat toxic to the kidneys, although this effect is small compared to the huge benefit they bring in suppressing the immune system.

But no matter how good the tissue match, the pills don’t stop the immune system rejecting the new organ, they just slow it down, so eventually, the graft is rejected and the kidney fails.

Also, immune-suppressing drugs don’t always work, and the graft deteriorates, leaving the patient back on the waiting list for another kidney or consigned to a lifetime of dialysis.

Scientists have been trying to find ways to stop the rejection without the need for lifelong medication for some time. Strober started working on mice 30 years ago and has been trying ever since to get just the right mix of ingredients.

In their letter to the NEJM, Strober and colleagues describe a post-transplant immune tolerance treatment comprising injections of blood-forming stem cells from the kidney donor, radiation treatment, and antibodies that target the recipient’s own immune system:

“… a donor-cell infusion of highly enriched CD34+ hematopoietic progenitor cells mixed with CD3+ T cells, and a conditioning regimen of total lymphoid irradiation and anti-T-cell antibodies …”

They treated 12 patients who received matched kidney transplants with this protocol. Eight of them have now been off immunosuppressants for at least one year and in some cases more than three years. There appears to be no damage to their new kidney, unlike conventional transplants.

None of the 12 patients has shown signs of kidney transplant failure or serious side effects. The researchers reported the withdrawal of drugs from the first patient in the NEJM in 2008, and Thursday’s letter to the editor reports that the success with that patient has been reproduced.

Strober said the recipient’s immune system appears to return to its pre-transplant state of readiness but “casts a blind eye on the foreign tissue of the graft”.

The radiation treatment carefully targets the patient’s lymph nodes, spleen and thymus to temporarily weaken their own immune systems. Then they are injected with stem cells drawn from the kidney donor. These eventually differentiate to team up with the recipient immune system to form one that is now more receptive to the new organ compared to what is seen in conventional post -transplant treatment.

The letter concludes:

“… the majority of patients were able to discontinue antirejection medications, and all patients had excellent graft function at the last observation point.”

The researchers are recruiting more patients on the study, and plan to include some less than perfectly matched donor-recipient pairs:

“We are applying the protocol to patients who were mismatched for one HLA haplotype on the basis of the safety profile of the current study,” they write.

The study is funded by grants from the National Institutes of Health.

Written by Catharine Paddock PhD