C - Chemistry – Metallurgy – 07 – K
Patent
C - Chemistry, Metallurgy
07
K
C07K 16/30 (2006.01) A61K 38/00 (2006.01) A61K 38/43 (2006.01) A61K 39/00 (2006.01) A61K 39/395 (2006.01) C07K 14/00 (2006.01) C07K 14/735 (2006.01) C07K 16/32 (2006.01)
Patent
CA 2399940
The present invention is related to enhancing the function of anti-tumor antibodies by regulating Fc.gamma.RIIB-mediated activity. In particular, disrupting SHIP activation by Fc.gamma.RIIB enhances cytotoxicity elicited by a therapeutic antibody in vivo in a human. The invention further provides an antibody, e.g., an anti-tumor antibody, with a variant Fc region that results in binding of the antibody to Fc.gamma.RIIB with reduced affinity. A variety of transgenic mouse models demonstrate that the inhibiting Fc.gamma.RIIB molecule is a potent regulator of cytotoxicity in vivo.
La présente invention concerne l'amélioration de la fonction des anticorps antitumoraux par régulation de l'activité associée au Fc.gamma.RIIB. En particulier, l'interruption de l'activation SHIP par le Fc.gamma.RIIB favorise la cytotoxicité déclenchée par un agent thérapeutique in vivo chez un humain. L'invention concerne également un anticorps, par exemple, un anticorps antitumoral, avec une région Fc variante permettant la liaison de l'anticorps au Fc.gamma.RIIB avec une affinité réduite. Une variété de modèles de souris transgéniques démontrent que la molécule F.gamma.cRIIB inhibitrice est un puissant régulateur de cytotoxicité in vivo.
Smart & Biggar
The Rockefeller University
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