VIP antagonist for the prevention of graft-vs-host disease.
- Short (6hrs) ex-vivo exposure to VIP antagonist sufficient to prevent cell conversion.
- Prevents graft-vs-host disease without immune suppression.
Graft-vs-host disease is an inflammatory disease unique to bone marrow transplant recipients and is the only transplant procedure in which the transplanted cells must accept the body rather than the body accepting the new cells. There are nearly 20,000 bone marrow transplants performed each year in the US for a variety of malignant and non-malignant conditions. Depending on how closely the donor and recipient are matched, 30-80% of transplants result in a graft-vs-host disease reaction and this disease causes of about 20% of deaths after transplant. Current treatment strategies rely on high doses of corticosteroids to suppress the immune system, which often results in deadly infections. Non immune-suppressant treatments are desperately needed as an alternative.
Graft-vs-host disease is thought to be a result of antigen presenting cells that are “cross-dressed”, or express both donor and recipient antigens. These cells efficiently present allo-antigen and can activate immune responses leading to graft rejection or graft-vs-host disease. Inhibiting the generation of these cross-dressed cells in vitro before a bone marrow transplant may prevent the initiation of graft-vs-host disease. Emory researchers have identified that treating bone marrow cells in vitro before a transplant with vasoactive intestinal peptide (VIP) antagonist inhibits the formation of cross-dressed cells. This discovery may provide a non immune-suppressant preventative of graft-vs-host disease.
This treatment strategy has been validated in a mouse model of bone marrow transplant.