B7 LIGANDS/CD20 INHIBITOR COMPOSITION AND USE THEREOF

摘要

A therapeutic composition is described that can be used for treating or prevention of diseases association with modulation of activity of human CD80 or human CD20. The disclosed invention is based, on engineering of a heterotrimeric protein assembly that is capable of simultaneous binding to human CD80 and human CD20 and attenuating their functions. The heterotrimeric protein assembly comprises an extracellular portions of human CTLA-4 and a heavy and a light chains of an anti-CD20 antibody, or their functional fragments. Each, the CTLA-4 portion and the anti-CD20 antibody portion, is fused to a distinct mutant of Fc portion of the human Ig Gamma- 1. The two distinct Fc mutants in the heterotrimeric protein assembly are engineered as to favor the heteromeric dimer formation between the two Fc mutants over any homomeric assembly. DNA expression vectors and expression systems for overproducing the polypeptides in mammalian cells are also provided for.