Anti-rejection medication and immunotherapy kicks cancer and protects kidney transplants (“Massive advancement” with nivolumab)

Adding immunotherapy to standard anti-rejection medication could change the lives of thousands of kidney transplant patients with incurable cancer, as research shows it can reduce this risk of organ rejection and eliminate cancer in a quarter of patients.

The world-first study showed that a dual combination of transplant anti-rejection drugs and immune checkpoint inhibitors not only reduced organ rejection rates to 12% (from 40–50%) but also eradicated cancer cells in 25% of patients.

Immune checkpoint inhibitors are drugs that block proteins called checkpoints. These checkpoints help keep immune responses from being too strong but can also keep T-cells from killing cancer cells. When these checkpoints are blocked, the T-cells can kill cancer cells more effectively.

Professor Rob Carroll says these findings are a gamechanger for kidney transplant patients with incurable cancer.

"Cancer is a leading cause of death in kidney transplant recipients with the rate of cancer being three-times higher in this group, than in the general population," Prof Carroll says.

"The terrible irony is that the immunosuppressants that patients must always take to stop their immune systems attacking their transplants, are also the medicines that stops the immune system getting rid of pre-cancer cells.

"To correct this imbalance, our study tested the efficacy of maintaining baseline anti-rejection drugs (to protect the transplant) and adding immune checkpoint inhibitors (to attack the cancer).

"The patients responded well with lower rates of organ rejection to 12%, compared to previous reports and eliminating cancers cells in 25% of patients.

"It's a massive advancement for kidney transplant patients; a whole new lease on life."

The study assessed 22 patients with a renal transplant and incurable locally advanced or metastatic cancer that had progressed despite first-line standard anti-tumor treatment. They kept their standard anti-rejection drugs unchanged and were treated with an immune checkpoint inhibitor, nivolumab.

March 2007 STANFORD, Calif. - Researchers at Stanford University Medical Center have discovered a way to transplant kidneys without having the patient remain on a lifelong course of immune-suppressing drugs in order to prevent rejection. As an added bonus, the donor kidneys don't even need to come from a relative - a restriction that has severely limited kidney availability to sick people in need.

Research results from four patients in the groundbreaking study will be presented April 28 in Washington, DC, at the American Transplant Congress by Maria Millan, MD, transplant surgeon at Stanford Hospital & Clinics and assistant professor of surgery. The work is also scheduled to be published in the journal Transplantation May 15.

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.

Strober said so far, two of the four patients in the study are completely free of drugs, with another still tapering off. This new approach to kidney transplantation began in the usual way, 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 combined 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. After this procedure, the recipient's immune cells recognize the donor's organ as friend rather than foe.

The Stanford team monitored the recipient's new hybrid immune system looking for a mixture of cells from both the recipient and the donor. These cells were tested in the laboratory and did not attack cells taken from the donor. This told the team that the new hybrid immune system would not mount an attack against the transplanted organ. At this time, the team slowly weaned the patient away from the immune-suppressive drugs.

http://www.sciencedaily.com/releases/2002/04/020424072642.htm

Disclaimer: Opinions posted on Free Republic are those of the individual posters and do not necessarily represent the opinion of Free Republic or its management. All materials posted herein are protected by copyright law and the exemption for fair use of copyrighted works.