Approaches To Allogeneic Chimerism For The Induction Of Transplantation Tolerance
Funder
National Health and Medical Research Council
Funding Amount
$212,036.00
Summary
All patients with organ failure who receive a transplant require lifelong immunosuppressive medications to prevent the body from rejecting the foreign tissue. Indefinite immunosuppressive therapy is associated with significant side-effects which include infections and cancers. In addition, long-term loss of the transplants due to slow rejection (chronic rejection) remains high. Achieving a state of immunological tolerance in which transplanted tissue is regarded as self, but reactivity to all ot ....All patients with organ failure who receive a transplant require lifelong immunosuppressive medications to prevent the body from rejecting the foreign tissue. Indefinite immunosuppressive therapy is associated with significant side-effects which include infections and cancers. In addition, long-term loss of the transplants due to slow rejection (chronic rejection) remains high. Achieving a state of immunological tolerance in which transplanted tissue is regarded as self, but reactivity to all other foreign tissues (e.g. harmful viruses, bacteria) remain normal, would solve all these problems. Tolerance would eliminate the need for immunosuppressive medications and prevent rejection of transplanted organs. The production of mixed bone marrow chimerism is a potent method of inducing tolerance. Chimerism is a state in which bone marrow tissue from two genetically different individuals coexists in one person. This can be achieved by bone marrow transplantation from a specific donor, and if chimerism is achieved, the recipient will accept all tissues from the bone marrow donor without the need for ongoing immunosuppressive therapy. This study will attempt to examine the use of different therapeutic reagents (e.g. antibodies alone or antibodies linked to idarubicin, a drug which prevent cells dividing) to develop safe protocols for the production of bone marrow chimerism and tolerance for routine clinical use in humans. The study will also examine different cellular components of the donor bone marrow which may induce tolerance.Read moreRead less