Future of monoclonal antibodies in solid organ transplantation

The ultimate objective of immunosuppressive therapy is to block transplant recipient reactivity to allograft incompatibilities while sparing other responses. Increased clarification of rejection mechanisms has made possible the precise suppression of specific elements of the immune response using murine anti-human monoclonal antibodies. In addition, recombinant DNA technology has made available novel agents including "humanized," bispecific, or toxin-conjugated molecules, which avoid some of the limitations of murine reagents. Using such agents, donor-specific tolerance has been induced in experimental models after a limited course of therapy directed against selected effector cell surface-associated molecules such as CD4, CD25, and CD54. It remains to be determined how such observations can be successfully transferred to the human situation. It seems likely, however, that as new molecular agents are developed, increasingly effective suppression of specific cellular targets will become an essential element of clinical protocols. Such agents may provide long-term immunosuppression with limited periods of immunosuppressive agent administration.