Antibodies for Transplantation
The use of antibodies in transplantation has become a clinical reality. Antibodies have been used to both dampen the recipient’s immune response and to obscure the immunogenicity of the donor graft. Traditionally, antibodies have been administered to the
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10 Antibodies for Transplantation Denise L. Faustman 1. Introduction The use of antibodies in transplantation has become a clinical reality. Antibodies have been used to both dampen the recipient’s immune response and to obscure the immunogenicity of the donor graft. Traditionally, antibodies have been administered to the transplant recipient to transiently inactivate the host’s T cells, the lymphocytes responsible for recognizing and attacking foreign proteins, cells, and tissues. Antibodies can also be used to eliminate any highly immunogenic passenger cells from a donor graft prior to transplantation, and antibodies can mask or conceal antigens present on donor cells that might trigger rejection. In addition to enhancing the survival of grafts in the clinic, antibodies are adding to our basic understanding of the molecular mechanisms responsible for transplant rejection. Antibodies designed to recognize various components of the immune system have helped to clarify the role that host T cells and cells in donor transplant play in the rejection cascade. 2. A Host of Antibodies; Meet the Antibodies Systemically administered antibodies have been used for decades to promote the survival of transplanted tissues and organs. The first preparations, given to the recipients of kidney transplants, contained polyclonal antisera directed against lymphocytes. Administered in conjunction with immunosuppressive drugs, the antibodies temporarily deplete the lymphocytes in the recipient, allowing the graft to take hold before the immune system kicked in. However, these antibodies were nonspecific, and combined with pharmacologic immunosuppression would leave recipients susceptible to infections. From: Methods in Molecular Medicine, Vol. 40: Diagnostic and Therapeutic Antibodies Edited by: A. J. T. George and C. E. Urch © Humana Press Inc., Totowa, NJ
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More recently monoclonal antibodies (mAbs) have been directed against specific proteins on the surface of T cells. The most famous commercial preparation, OKT3 made by Ortho (Raritan, NJ), targets the CD3 receptor on T cells, which has allowed better quality control and fewer side effects. Administered to the recipient prior to transplantation or during a rejection episode, this antibody depletes the host’s cytotoxic T lymphocytes. The large-scale production of pure mAbs, such as OKT3, was made possible by the development of hybridoma technology, which allowed the fusion of immortalized lymphoma cells with antibody-producing spleen cells (1). Generally speaking, polyclonal antibody preparations react most strongly with host lymphocytes because they recognize more cell types and a larger number of markers per cell. At the same time, polyclonal antibodies show greater batch-to-batch variability. Monoclonal antibodies, on the other hand, are restricted in that they recognize only one type of marker on a cell, but they are more uniform in their properties and show less variability then polyclonal preparations. In addition to choosing between polyclonal versus m
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