Figure 917

New immunosuppressive agents. New agents such as mycophenolate mofetil, FK506, and rapamycin are currently under evaluation for refractory acute rejection. In addition, both mycophenolate and rapamycin prevent chronic allograft rejection in experimental animals. Whether this important observation is reproducible in humans remains to be determined by long-term study.

A, Humanized monoclonal antibodies. The development of genetically engineered humanized monoclonal antibodies will largely eliminate the anti-antibody response, thereby increasing the utility of anti-T-cell antibodies in the treatment of recurrent rejection. Experimental antibody therapies are now being designed to directly target the CD4 molecule, the interleukin-2 receptor, the CD3 molecule by a humanized form of monoclonal anti-CD3, and adhesion molecules such as intercellular adhesion molecule-1 or leukocyte function-associated antigen-1 [23]. Humanized monoclonal antibodies are essentially human immunoglobulin G (IgG), nonimmunologic with a long half-life, and potentially can be administered intravenously about every 2 weeks. Humanized anti-CD25 (IL-2 receptora chain) monoclonal antibodies has been shown to be effective in lowering the incidence of acute renal allograft rejection. Its role in the treatment of rejection, however, has not been explored. With increasing specificity for lymphocytes, these new agents are likely to have fewer toxicities and better efficacy.

B, Therapeutic application of CTLA41g to transplant rejection. APC—antigen-presenting cell; MHC—major histocompatibility complex; TCR—T-cell receptor.

0 0

Post a comment