Optimized Fc variants and methods for their generation
The present invention relates to optimized Fc variants, methods for their generation, and antibodies and Fc fusions comprising optimized Fc variants.
1. A method of mediating antibody-dependent cell-mediated cytotoxicity (ADCC) in a human comprising administering to a human a composition comprising a variant antibody of a parent antibody which variant mediates antibody-dependent cell-mediated cytotoxicity (ADCC) in the presence of human peripheral blood mononuclear cells more effectively than the parent antibody, wherein said variant comprises 239D/332E/330L substitutions in the Fc region, wherein numbering is according to the EU index.
2. The method according to claim 1 , wherein said parent antibody is selected from the group consisting of a human antibody, a humanized antibody, and a monoclonal antibody.
3. The method according to claim 1 or 2 , wherein said antibody comprises an IgG1 region.
4. The method according to claim 1 or 2 , wherein said variant antibody has specificity for a target antigen selected from the group consisting of Alpha5betalintegrin, CDI9, CD20, CD22, CD30, CD33, CD40, CD40L, CD52, Her2/neu, EGFR, EpCAM, MUCI, GD3, CEA, CA 125, HLA-DR, TNFalpha, MUCI8, prostate specific membrane antigen (PMSA) and VEGF.