Each year patients are prohibited from receiving a potentially life-saving organ transplant because of a pre-existing antibody directed against the donor's cell surface human leukocyte antigens (HLA). Such patients are considered “sensitized” to their donor organ, which may be the result of previous transplantations, pregnancy, and/or blood transfusions. The presence of certain donor-specific antibodies (DSA) is a contraindication to transplantation regardless of other factors that may indicate a donor match. DSA presence may cause hyperacute (immediate) antibody-mediated rejection (AMR) of the donor organ post-transplantation and possible loss of the donated organ. Patients having DSA (i.e., sensitized patients) thus spend a significantly longer time waiting for an acceptable donor organ. Thus, sensitized patients face not one, but at least two hurdles to organ donation: (1) blood type compatibility, and (2) sensitization. Furthermore, some patients may develop antibodies to their donor organ after transplantation, and such DSA is termed “de novo.” It is now known that a majority of patients that lose their transplant to chronic rejection do so as a result of de novo DSA.
At present, there are few treatment options available to sensitized patients with antibody mediated rejection. The treatments available include, for example, rituximab, and plasmapheresis with, or without, intravenous immunoglobulin (IVIg).
Although the treatments available show varying effectiveness for treating AMR initially, their effects become diminished and are not sustained in nearly half of patients. Thus, the long term effect of currently available treatments is poor and an enormous unmet need exists in the field for efficacious treatments of AMR and treatments and compositions that improve overall transplant survival for patients receiving cross-match positive organ transplants.