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Cancer drug effectively treats transplant rejections
December 29, 2008CINCINNATI-University of Cincinnati (UC) researchers have discovered a new therapy for transplant patients, targeting the antibody-producing plasma cells that can cause organ rejection.
Results of the study are published in the Dec. 27, 2008, edition of the journal Transplantation.
Steve Woodle, MD, and colleagues found that a cancer drug-bortezomib-used to treat multiple myeloma, or cancer of the plasma cells, is effective in treating rejection episodes caused by antibodies that target transplanted kidneys and reversing rejection episodes that did not respond to standard therapies.
B-lymphocytes, or B cells, play a large role in the humoral immune response by making immune proteins that attack transplanted organs.
"We found a body of literature demonstrating that bortezomib works well in suppressing transplant rejection in the laboratory," says Woodle, lead author of the study and chief of transplant surgery at UC. "Moreover, it worked well in models of autoimmune diseases."
T-lymphocytes, or T cells, are white blood cells that were commonly thought to cause the rejection of transplanted organs.
Woodle and his team began searching for agents that targeted plasma cells in 2005.
"It has become clear that plasma cells and the antibodies they produce play a bigger role in rejection than previously thought, and the development of therapies targeting these cells has lagged," he says. "We realized that current therapies don't target the plasma cells which may produce the antibody, in general."
Researchers administered this drug to six kidney transplant recipients with treatment-resistant organ rejection, evaluating and recording their responses to the treatment.
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, a board-certified oncology pharmacist in the division of transplant surgery 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.
"We are pleased to see its toxicities are similar in transplant recipients suffering from treatment-resistant mixed organ rejection," he adds. "We hope it will be a viable therapeutic treatment option in this patient group."
Woodle says although this data is promising, it is difficult to overestimate the implications of this drug.
"We have an immunosuppressive agent that for the first time can target antibody-producing plasma cells with an efficacy similar to drugs that target T cells," he says. "This has significant implications for transplantation and auto immune disease."
UC researchers are currently conducting four industry-supported clinical trials to expand these findings.
University of Cincinnati
B-lymphocytes, or B cells, play a large role in the humoral immune response by making immune proteins that attack transplanted organs.
"We found a body of literature demonstrating that bortezomib works well in suppressing transplant rejection in the laboratory," says Woodle, lead author of the study and chief of transplant surgery at UC. "Moreover, it worked well in models of autoimmune diseases."
T-lymphocytes, or T cells, are white blood cells that were commonly thought to cause the rejection of transplanted organs.
Woodle and his team began searching for agents that targeted plasma cells in 2005.
"It has become clear that plasma cells and the antibodies they produce play a bigger role in rejection than previously thought, and the development of therapies targeting these cells has lagged," he says. "We realized that current therapies don't target the plasma cells which may produce the antibody, in general."
Researchers administered this drug to six kidney transplant recipients with treatment-resistant organ rejection, evaluating and recording their responses to the treatment.
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, a board-certified oncology pharmacist in the division of transplant surgery 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.
"We are pleased to see its toxicities are similar in transplant recipients suffering from treatment-resistant mixed organ rejection," he adds. "We hope it will be a viable therapeutic treatment option in this patient group."
Woodle says although this data is promising, it is difficult to overestimate the implications of this drug.
"We have an immunosuppressive agent that for the first time can target antibody-producing plasma cells with an efficacy similar to drugs that target T cells," he says. "This has significant implications for transplantation and auto immune disease."
UC researchers are currently conducting four industry-supported clinical trials to expand these findings.
University of Cincinnati
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For the first time, researchers at Fred Hutchinson Cancer Research Center have reported the use of a radiolabeled antibody to deliver targeted doses of radiation, followed by a stem cell transplant, to successfully treat a group of leukemia and pre-leukemia patients for whom there previously had been no other curative treatment options.
Gastroenterology/hepatology societies release report evaluating fellowship training curriculum
Due to the increasing complexities of treating digestive diseases, allowing gastroenterological (GI) trainee physicians the opportunity to develop enhanced abilities and experiences in specific disease areas or procedures will be a great benefit to patients, according to a "Report of the Multisociety Task Force on GI Training."
Immune therapy can protect against or treat later lymphoma
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Switching immunosuppressants reduces cancer risk in kidney
Switching to a newer type of immunosuppressant drug may reduce the high rate of skin cancer after kidney transplantation, according to research being presented at the American Society of Nephrology's 42nd Annual Meeting and Scientific Exposition in San Diego, CA.
Immunotherapy demonstrates long-term success in treating lymphoma
Targeted immunotherapy has been an attractive new therapeutic area for a number of cancers because it has the potential to destroy tumor cells without damaging surrounding normal tissue. New study results demonstrate high success rates using specialized white blood cells to prevent or treat lymphoma associated with the Epstein-Barr virus (EBV-lymphoma) in patients who have received a hematopoietic stem cell transplant (HSCT).
Kidney transplants generally safe for lupus patients
Individuals with a history of lupus who receive a kidney transplant rarely develop the serious inflammatory condition lupus nephritis in their new organ, according to a paper being presented at the American Society of Nephrology's 42nd Annual Meeting and Scientific Exposition in San Diego, CA.
Extending treatment after liver transplant may benefit patients with hepatitis C recurrence
Extending hepatitis C treatment for liver transplant patients beyond current practice results in high rates of clearance of the hepatitis C virus from the blood, as well as a low rate of relapse, according to a Henry Ford Hospital study.
Researchers find brain cell transplants help repair neural damage
A Swiss research team has found that using an animal's own brain cells (autologous transplant) to replace degenerated neurons in select brain areas of donor primates with simulated but asymptomatic Parkinson's disease and previously in a motor cortex lesion model, provides a degree of brain protection and may be useful in repairing brain lesions and restoring function.
Placental precursor stem cells require testosterone-free environment to survive
Trophoblast stem cells (TSCs), cells found in the layer of peripheral embryonic stem cells from which the placenta is formed, are thought to exhibit "immune privilege" that aids cell survivability and is potentially beneficial for cell and gene therapies.
UT Southwestern patient first in North Texas to receive newest-generation heart failure device
UT Southwestern Medical Center patient Michael LeBlanc, 40, is the first in North Texas to receive the newest generation of a mechanical device designed to improve heart function. It will be his lifeline while he awaits a heart transplant.
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