New therapy for transplant rejection

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Researchers in the U.S. have discovered a new cancer drug which effectively treats transplant rejections.

The researchers from the University of Cincinnati (UC) say the new therapy for transplant patients, targets the antibody-producing plasma cells that can cause organ rejection.

According to a study by Dr. Steve Woodle and colleagues, the cancer drug bortezomib which is used to treat multiple myeloma, or cancer of the plasma cells, is also effective in treating rejection episodes caused by antibodies that target transplanted kidneys and the drug is able to reverse rejection episodes that do not respond to standard therapies.

Dr. Woodle, the lead author of the study and chief of transplant surgery at UC, says that they found evidence from other research that bortezomib works well in suppressing transplant rejection in the laboratory and also worked well in models of autoimmune diseases.

T-lymphocytes, or T cells, are white blood cells that are thought to cause the rejection of transplanted organs and Dr. Woodle and his team began searching for agents that targeted plasma cells in 2005.

Dr. Woodle says it is clear that plasma cells and the antibodies they produce play a bigger role in rejection than previously thought, and current therapies fail to target the plasma cells which may produce the antibody.

The researchers gave the drug to six kidney transplant recipients with treatment-resistant organ rejection and in each case, treatment with the drug provided prompt rejection reversal, prolonged reductions in antibody levels and improved organ function with suppression of recurrent rejection for at least five months.

Jason Everly, an oncology pharmacist at UC and co-author of the study, says the toxicities associated with this drug were predictable and manageable and were much less than those associated with other anti-cancer agents and they hope it will be a viable therapeutic treatment option for such patients.

Woodle says although this data is promising, it is difficult to overestimate the implications of this drug - the researchers are currently conducting four industry-supported clinical trials to expand these findings.

When a transplanted organ or tissue fails to be accepted by the body of the transplant recipient transplant rejection occurs; this happens because the immune system of the recipient attacks the transplanted organ or tissue, which is to be expected, because the immune system is designed to distinguish foreign material within the body and attempt to destroy it, just as it attempts to destroy infecting organisms such as bacteria and viruses.

Rejection can occur immediately following surgery, within the first three months after transplantation but can also occur months or years after transplantation.

A single episode of acute rejection is not a cause for concern if recognised and treated promptly, and rarely leads to organ failure but repeated or prolonged episodes are more of a worry.

Transplant rejection can be treated using chemotherapeutic drugs designed to suppress the immune system but such drugs also carry risks - they have toxic effects on organs and can cause severe infections.

If a bone marrow transplant can be performed, the transplant recipient’s immune system can be replaced with the donor’s immune system, thus enabling the recipient’s body to accept the new organ without risk of rejection.

Sydney girl Demi-Lee Brennan made history when after a liver transplant when she was nine her blood type changed and adopted the immune system of her donor - her body no longer attempts to reject the transplanted liver and she does not need immunosuppressant medication.

Doctors at Sydney’s Westmead Children’s Hospital say her case is unique.

Results of the UC study are published in the Dec. 27, 2008, edition of the journal Transplantation.


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