Keeping bone marrow transplants safe

U. MICHIGAN (US) — Researchers have discovered a new method to prevent the immune-system attacks that often occur following bone marrow transplants.

Bone marrow transplantation can cure patients with leukemia and other cancers even when the disease is resistant to other treatments.

The success of this procedure relies on killing cancer cells by using immune cells from a bone marrow donor while avoiding an immune attack against the patient’s organs, which causes a dangerous complication called graft-versus-host disease.

Researchers are encouraged by preliminary results in mouse models that work by inhibiting the Notch signaling pathway in immune cells called donor T lymphocytes.

“Notch is an important pathway that researchers have started to identify multiple functions for in normal tissues and in cancer,” says Ivan Maillard, professor of the Life Sciences Institute and assistant professor of internal medicine at the University of Michigan.

The work, done in collaboration with a team at the University of Michigan Comprehensive Cancer Center, was recently reported in the journal Blood.

Maillard’s team found that Notch-deficient T cells had a markedly reduced ability to produce inflammatory mediators and to damage the normal organs of the recipient mice.

However, unlike previous interventions, Notch inhibition had selective effects and did not cause global immunosuppression.

In particular, the Notch-deficient T cells remained able to efficiently kill cancer cells, resulting in the elimination of the tumor cells without causing life-threatening graft-versus-host disease.

Researchers say they are developing an expanding set of reagents to target components of Notch signaling that can someday be developed into effective new therapies for patients.

This work was supported by an Innovation Award from the Damon Runyon Cancer Research Foundation, the American Society of Hematology, and the University of Michigan Comprehensive Cancer Center.

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