| abstract |
FIELD: medicine; oncology. n SUBSTANCE: present invention relates to combined therapy of malignant tumors. That is ensured by introducing variant 4D5 chimeric antibody in combination with a molecule which specifically binds a cell surface receptor or a ligand thereof which regulates an immune control point. 4D5 antibody contains a variable light chain domain comprising the amino acid sequence SEQ ID NO: 4, and heavy chain, which contains a variant Fc-site exhibiting increased ADCC activity, wherein the heavy chain contains an amino acid sequence selected from a group consisting of SEQ ID NO: 9, SEQ ID NO: 11 and SEQ ID NO: 13. A molecule which specifically binds a cell surface receptor comprises a variant Fc region having at least one modification relative to the wild-type IgG1 Fc region or the IgG4 Fc region, wherein said variant Fc region of said molecule exhibits reduced ADCC activity with respect to a comparable molecule which contains wild-type IgG1 Fc region. n EFFECT: combined administration of said agents provides effective treatment of tumors expressing HER2/neu, including refractory to trastuzumab therapy. n 28 cl, 7 tbl, 8 ex, 15 dwg |