Identification and engineering of antibodies with variant Fc regions and methods of using same

摘要

The present invention relates to molecules, particularly polypeptides, more particularly immunoglobulins (e.g., antibodies), comprising a variant Fc region, wherein said variant Fc region comprises at least one amino acid modification relative to a wild-type Fc region, which variant Fc region binds FcγRIIIA and/or FcγRIIA with a greater affinity, relative to a comparable molecule comprising the wild-type Fc region. The molecules of the invention are particularly useful in preventing, treating, or ameliorating one or more symptoms associated with a disease, disorder, or infection. The molecules of the invention are particularly useful for the treatment or prevention of a disease or disorder where an enhanced efficacy of effector cell function (e.g., ADCC) mediated by FcγR is desired, e.g., cancer, infectious disease, and in enhancing the therapeutic efficacy of therapeutic antibodies the effect of which is mediated by ADCC.

主权项

1. A method of enhancing antibody-dependent cell mediated cytotoxicity (ADCC) in a patient having a cancer characterized by a cancer antigen, said method comprising administering to said patient a therapeutically effective amount of a polypeptide having a variant Fc region, wherein said variant Fc region:
(A) contains a CH2 domain and a CH3 domain; and (B) possesses an amino acid sequence that differs from the amino acid sequence of a wild-type Fc region by comprising amino acid modifications R292P and V3051, relative to said wild-type Fc region, wherein said numbering is that of the EU index as in Kabat.