H. Lee Moffitt Researchers Discover Potential Targets To Reduce Risk Of Stem Cell Transplants

Main Category: Lymphoma / Leukemia / Myeloma
Also Included In: Cancer / Oncology;  Blood / Hematology;  Stem Cell Research
Article Date: 21 Feb 2007 - 0:00 PDT

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Inhibiting one gene -- even temporarily -- can improve cure rates for blood cancer patients who receive stem cell transplants. This strategy may also help patients with genetic and autoimmune diseases who are also treated with stem cell transplants.

Researchers at H. Lee Moffitt Comprehensive Cancer Center in Tampa, led by William Kerr Ph.D., and funded by The Leukemia & Lymphoma Society, have discovered that the SHIP gene plays a critical role in graft vs. host disease (GvHD), in which a donor's immune cells (the "graft") attack a stem cell transplant patient's healthy tissue (the "host") as well as cancer cells. By using genetically engineered mice, the researchers have shown that inactivating the SHIP gene for just one week protects transplant recipients from acute GvHD. This protection is seen even when the graft contains extra immune cells to help the graft "take" or when the graft cells are completely mismatched to the recipient. The findings will be published in the March 1st issue of the "Journal of Immunology."

Allogeneic transplants are the best curative option for many blood cancer patients because the donor's cells replace critical blood cells lost during a patient's pre-transplant chemotherapy, and because the donor's cells can help kill any remaining cancer cells to prevent relapse. But, poorly matched donor grafts can be rejected, just as in organ transplants, or cause GvHD. "Currently, suitable donors can only be found for 20 to 30 percent of patients who might be cured by allogeneic transplants," said Kerr. "But by learning which genes control graft rejection and GVHD, new targeted treatments might be used to make transplants successful and safe for more patients."

Since the SHIP gene is also present in humans, Dr. Kerr says the team's findings are important for cancer patients. Kerr said that with adequate funding, clinical trails using SHIP-targeting strategies in human patients could only be a few years away.

"If we can identify approaches to inhibit SHIP in patients, then we could potentially reduce the risk of GVHD in matched transplants that are currently used to treat blood cancer patients, perform allogeneic transplants even when a matched donor cannot be found, and increase the number of donor immune cells that can be given to patients post-transplant to combat cancer relapse," Kerr said.

SHIP inhibitor drugs are already being developed and Dr. Kerr has shown that a genetic treatment strategy called RNA interference (RNAi) can also be used to turn the SHIP gene off. Other scientists have shown that RNAi can be used to turn-off specific genes in mice and non-human primates.

Kerr is a recipient of the Society's Scholar Award -- a program that provides funding to highly qualified investigators conducting original research on leukemia, lymphoma or myeloma.

About The Leukemia & Lymphoma Society

The Leukemia & Lymphoma Society(R), headquartered in White Plains, NY, with 66 chapters in the United States and Canada, is the world's largest voluntary health organization dedicated to funding blood cancer research and providing education and patient services. The Society's mission: Cure leukemia, lymphoma, Hodgkin's disease and myeloma, and improve the quality of life of patients and their families. Since its founding in 1949, the Society has invested more than $486 million in research specifically targeting leukemia, lymphoma and myeloma. Last year alone, the Society made 4.2 million contacts with patients, caregivers and healthcare professionals.

For more information about blood cancer, visit http://www.LLS.org or call the Society's Information Resource Center (IRC), a call center staffed by master's level social workers, nurses and health educators who provide information, support and resources to patients and their families and caregivers.

The Leukemia & Lymphoma Society
http://www.LLS.org

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