Monoclonal antibody therapy for the induction of transplantation tolerance

Abstract

There are three ways in which monoclonal antibodies could be used to facilitate the induction of tolerance to foreign tissues after organ transplantation. First, depleting monoclonal antibodies could be directed against the T cells responsible, thereby reducing their number and acting to non-specifically immunosuppress the patient. This is generally not sufficient to allow tolerance induction in the T cells which repopulate the periphery. Second, depleting monoclonal antibodies could be used to remove donor passenger leukocytes and antigen-presenting cells from the donor organ, which may both reduce immunogenicity and increase the chance of tolerance induction. Third, non-depleting, but functionally blocking, monoclonal antibodies to T cell molecules such as CD4 and CD8 can allow the specific induction of transplantation tolerance in mouse models, an approach which might be applicable to man, not only for organ transplantation, but also in the treatment of autoimmune diseases. These three approaches are, in time, likely to complement each other in clinical practice. Monoclonal antibodies can be tailored to each approach by choosing appropriate specificities and isotypes, and further refinements can be made where necessary by making monovalent or humanised antibodies. The application of each of these approaches to clinical therapy is described.