IMMUNE RECEPTORS - TARGETS FOR THERAPY OF LEUKEMIA LYMPHOMA, AUTOIMMUNE-DISEASES AND FOR THE PREVENTION OF ALLOGRAFT-REJECTION

Immune receptor-directed therapy has been applied clinically to an array of human disorders. However, effective therapy using unmodified murine monoclonal antibodies was elusive because these antibodies are immunogenic and elicit a human immune response, are not cytocidal against human cells, and in most cases are not directed against a cell surface structure required for proliferation and survival. Recently therapy mediated by monoclonal antibodies has been revolutionized by the definition of cell surface structures as targets for effective monoclonal antibody action, the creation by genetic engineering of less immunogenic and more effective monoclonal antibodies, and by the arming of such antibodies with toxins and radionuclides. Furthermore, other therapeutic agents directed toward immune receptors have been developed, including cytokine-toxin fusion proteins as alternative vehicles to address abnormal receptor-expressing cells, soluble immune receptors and naturally occurring receptor antagonists as immunomodulators, and T cell antigen receptor peptides as immunogens to provide protection against autoimmune diseases. Thus, the new insights concerning the structure and function of lymphocyte cell surface receptors and the development of different modalities of receptor-specific therapy are providing new perspectives for the treatment of human leukemia/lymphoma, autoimmune and graft-vs-host diseases, and for the prevention of allograft rejection.