Use of a cd40: cd154 link switch to prevent inappropriate immune responses, particularly graft rejection

摘要

B "USE OF A CD40 CONNECTION SWITCH: CD154 TO AVOID IMPROPER IMMUNE RESPONSES, PARTICULARLY GRAFT REJECTION" D. Compositions and methods disclosed herein capitalize on the discovery that rejection of a tissue graft can be inhibited using a CD40: CD154 link switch, either individually or in combination with another immunity modulator or immunosuppressant. An advantageous synergistic combination includes a CD40: CD154 link switch and a CD28 signal switch. An example CD40: CD154 binding switch is an anti-CD154 monoclonal antibody, such as an antibody having the specific antigen binding characteristics of monoclonal antibody 5c8. An CD28 signaling switch taken as an example is a CTLA4-Ig fusion protein. The disclosed compositions and methods can unexpectedly be used to prolong the survival of grafted tissue in a recipient host, in order to reverse an acute graft rejection and also to attenuate the immunological consequences regarding the deficiency of the grafted tissue.