Antigen-binding molecule containing modified Fc region

A method of treating a tumor in a subject, the method comprising

• identifying the subject as having a tumor that expresses a first antigen, and
• administering an antibody comprising an antibody variable region that binds to the first antigen and an Fc region dimer comprising a first IgG1 Fc region and a second IgG1 Fc region,
• wherein the first and second IgG1 Fc regions each comprise a CH2 domain;
• wherein the CH2 domain of either or both of the first and second IgG1 Fc regions comprises an antigen-binding site that binds to a second antigen different from the first antigen;
• wherein the antigen-binding site is within loop 2, loop 3, or loop 4 of one of the CH2 domains;
• wherein the second antigen is a molecule naturally expressed on an immunocyte or on both a tumor cell and a normal cell, and is not an FcγR;
• wherein the Fc region dimer comprises an FcγR-binding site that binds to FcγRIIIa;
• wherein the Fc region dimer does not bind to both the second antigen and FcγRIIIa at the same time;
• wherein the antibody can treat the tumor (A) by crosslinking a tumor cell and the immunocyte, or (B) by crosslinking a tumor cell and a cell expressing FcγRIIIa, or both (A) and (B);
• wherein each of the following EU numbering positions in the first IgG1 Fc region is occupied by the amino acid residue specified for that position:
• position 234:
• Tyr,
• position 236:
• Trp, and
• position 298:
• Ala;
• and
• wherein each of the following EU numbering positions in the second IgG1 Fc region is occupied by the amino acid residue specified for that position:
• position 239:
• Asp,
• position 330:
• Leu, and
• position 332:
• Glu.