Two unsolved problems in organ transplantation are 1) injury caused by antibody directed at the donor organ; and 2) recurrence of autoimmune disease after transplantation. Neither of these immunologic injuries is well addressed by current immunosuppressive therapy, and both prevent successful long-term allograft function. Our laboratory works in animal models to address the first of these problems and is engaged in human clinical trials to address the second.
Two strategies that we have considerable published experience include lymphocyte depletion and costimulation blockade. At this time we are particularly focused on strategies to address the B cell or plasma cell responsible for producing antibodies. We are developing strategies to safely lower the level of antibody in pre-sensitized hosts to permit successful transplantation in the setting of prior immunization to donor MHC antigens.