Use of a cd40:cd154 binding interruptor to prevent counter...

A - Human Necessities – 61 – K

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Details

A61K 39/395 (2006.01) A61K 31/445 (2006.01) A61K 31/57 (2006.01) A61K 38/13 (2006.01) A61K 38/17 (2006.01) C07K 14/705 (2006.01) C07K 16/28 (2006.01) A61K 38/00 (2006.01)

Patent

CA 2291156

Compositions and methods disclosed herein capitalize on the discovery that rejection of a tissue graft can be inhibited using a CD40:CD154 binding interruptor, either alone or in combination with another immunomodulator or immunosuppressor. An advantageous, synergistic combination includes a CD40:CD154 binding interruptor and a CD28 signalling interruptor. An exemplary CD40:CD154 binding interruptor is an anti-CD154 monoclonal antibody, such as an antibody having the antigen-specific binding characteristics of the 5c8 monoclonal antibody. An exemplary CD28 signalling interruptor is a CTLA4-Ig fusion protein. The disclosed compositions and methods unexpectedly can be used to prolong survival of grafted tissue in a recipient host, to reverse acute graft rejection, and to attenuate immunological consequences of the failure of grafted tissue.

L'invention concerne des compositions et des procédés qui s'appuient sur la découverte selon laquelle le rejet d'une greffe de tissu peut être inhibé au moyen d'un interrupteur de fixation CD40:CD154, qu'il soit utilisé seul ou associé à un autre immunomodulateur ou immunodépresseur. Un complexe médicamenteux favorable renferme un interrupteur de fixation CD40:CD154, ainsi qu'un interrupteur de signalisation CD28. Un anticorps monoclonal anti-CD154, tel qu'un anticorps présentant les caractéristiques de fixation spécifique d'antigène de l'anticorps monoclonal 5c8, constitue un exemple d'interrupteur de fixation CD40:CD154, une protéine de fusion CTLA4-Ig constituant un exemple d'interrupteur de signalisation CD28. Les compositions et les procédés de cette invention peuvent être utilisés pour prolonger la survie d'une greffe de tissu chez un receveur, pour renverser un rejet de greffe, et pour atténuer les conséquences immunologiques dues à l'échec d'une greffe.

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