Preparation of antibodies selective for activating Fc receptors, useful for treatment of tumors and viral or bacterial infections, by replacing specific histidine residues in the Fc region of a monoclonal antibody

摘要

Method for preparing antibodies (Ab) the Fc region of which binds selectively to receptors (FcR) for the Fc region of activating antibodies comprises selective replacement of specific amino acids : Method for preparing antibodies (Ab) the Fc region of which binds selectively to receptors (FcR) for the Fc region of activating antibodies comprises: (A) producing monoclonal antibodies (MAb) from a (hetero)hybridoma or any other animal, plant or human cell line; (B) replacing both His310 and His435 (Kabat numbering) in the Fc region of MAb by Lys, Ala, Gly, Val, Leu, Ile, Pro, Met, Trp, Phe, Ser or Thr; and (C) selecting altered MAb for which binding to inhibitory FcR is reduced by at least 30%, preferably 50-90 or more %, compared with the same MAb having the native Fc region. ACTIVITY : Cytostatic; Virucide; Antibacterial; Anti-HIV; Hepatotropic; Antiinflammatory; Tuberculostatic. MECHANISM OF ACTION : Antibody Therapy; Activation of immunological effector cells.