Monoclonal antibody treatment of human allograft recipients. 1988

F L Delmonico, and A B Cosimi
Transplantation Unit of the General Surgical Services, Massachusetts General Hospital, Boston 02114.

Antilymphocyte antibody immunosuppression has evolved to the use of therapeutic antibodies which are monoclonal in content. An antibody is termed monoclonal if each immunoglobulin molecule is produced by a single clone of cells and, thus, is identical in both the heavy and light chain structure to every other molecule in the preparation. Monoclonal preparations provide more consistent bioefficacy and predictable toxicity than do polyclonal products. Studies in nonhuman primate allograft recipients have established the immunosuppressive efficacy of several mAb. The results of pilot trial studies using a pan-T-cell mAb, OKT3, either prophylactically or at the time of acute rejection have revealed OKT3 to be remarkably immunosuppressive in man. OKT3 has subsequently been shown in multicenter, randomized trials to be more effective than conventional suppression in reversing renal and hepatic allograft rejection. In uncontrolled trial studies, similar efficacy in reversing cardiac rejection has been reported. Despite these impressive results, several limitations to OKT3 therapy persist. These include febrile and other systemic symptoms after the first or second infusion, a frequency of recurrent rejection episodes and the development of antibodies to the murine protein which may preclude subsequent treatment with the same mAb. Other murine mAb, such as CBL1 and anti-T12, have been noted to produce less side effects; however, these mAb have not been as effective. The next generation of mAb will be selected to minimize these limitations. It is anticipated that future mAb protocols will specifically suppress only selected subsets of T cells, and that these mAb may be chimeric or even human in structure to limit their immunogenicity.

UI MeSH Term Description Entries
D007165 Immunosuppression Therapy Deliberate prevention or diminution of the host's immune response. It may be nonspecific as in the administration of immunosuppressive agents (drugs or radiation) or by lymphocyte depletion or may be specific as in desensitization or the simultaneous administration of antigen and immunosuppressive drugs. Antirejection Therapy,Immunosuppression,Immunosuppressive Therapy,Anti-Rejection Therapy,Therapy, Anti-Rejection,Therapy, Antirejection,Anti Rejection Therapy,Anti-Rejection Therapies,Antirejection Therapies,Immunosuppression Therapies,Immunosuppressions,Immunosuppressive Therapies,Therapies, Immunosuppression,Therapies, Immunosuppressive,Therapy, Immunosuppression,Therapy, Immunosuppressive
D012008 Recurrence The return of a sign, symptom, or disease after a remission. Recrudescence,Relapse,Recrudescences,Recurrences,Relapses
D006084 Graft Rejection An immune response with both cellular and humoral components, directed against an allogeneic transplant, whose tissue antigens are not compatible with those of the recipient. Transplant Rejection,Rejection, Transplant,Transplantation Rejection,Graft Rejections,Rejection, Graft,Rejection, Transplantation,Rejections, Graft,Rejections, Transplant,Rejections, Transplantation,Transplant Rejections,Transplantation Rejections
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000328 Adult A person having attained full growth or maturity. Adults are of 19 through 44 years of age. For a person between 19 and 24 years of age, YOUNG ADULT is available. Adults
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D000911 Antibodies, Monoclonal Antibodies produced by a single clone of cells. Monoclonal Antibodies,Monoclonal Antibody,Antibody, Monoclonal
D013601 T-Lymphocytes Lymphocytes responsible for cell-mediated immunity. Two types have been identified - cytotoxic (T-LYMPHOCYTES, CYTOTOXIC) and helper T-lymphocytes (T-LYMPHOCYTES, HELPER-INDUCER). They are formed when lymphocytes circulate through the THYMUS GLAND and differentiate to thymocytes. When exposed to an antigen, they divide rapidly and produce large numbers of new T cells sensitized to that antigen. T Cell,T Lymphocyte,T-Cells,Thymus-Dependent Lymphocytes,Cell, T,Cells, T,Lymphocyte, T,Lymphocyte, Thymus-Dependent,Lymphocytes, T,Lymphocytes, Thymus-Dependent,T Cells,T Lymphocytes,T-Cell,T-Lymphocyte,Thymus Dependent Lymphocytes,Thymus-Dependent Lymphocyte
D014184 Transplantation, Homologous Transplantation between individuals of the same species. Usually refers to genetically disparate individuals in contradistinction to isogeneic transplantation for genetically identical individuals. Transplantation, Allogeneic,Allogeneic Grafting,Allogeneic Transplantation,Allografting,Homografting,Homologous Transplantation,Grafting, Allogeneic

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