Construction and application of bispecific antibody HER2xCD3
The present invention provides a bispecific antibody. The bispecific antibody provided by the present invention comprises a single-chain unit and a monovalent unit, wherein the single-chain unit has a specific binding capability against a surface antigen CD3 of an immune cell; the monovalent unit has a specific binding capability against a surface antigen HER2 of a tumor cell; the single-chain unit comprises a single-chain variable fragment ScFv fused with an Fc fragment; and the monovalent unit comprises a light chain and heavy chain pair. The present invention also provides a preparation method of the bispecific antibody and pharmaceutical use of these antibodies.
1. A bispecific antibody comprising:
(a) a monovalent unit comprising a light chain-heavy chain pair having specificity to a human tumor cell membrane surface antigen; and
(b) a single-chain unit comprising the amino acid sequence of SEQ ID NO: 5, wherein the single-chain unit has specificity to CD3.
2. The bispecific antibody of claim 1 , wherein the light chain binds to the heavy chain through a disulfide bond and the heavy chain binds to the single-chain unit through one or more disulfide bonds.
3. The bispecific antibody of claim 1 , which is a human or humanized antibody.
4. The bispecific antibody of claim 1 , wherein the human tumor cell membrane surface antigen is selected from the group consisting of HER2, CD20, CD30 and CD133.
5. A method of treating a human cancer patient having a tumor cell characterized with a tumor cell membrane surface antigen comprising administering to the patient a bispecific antibody comprising (a) a monovalent unit comprising a light chain-heavy chain pair having specificity to the tumor cell membrane surface antigen; and (b) a single-chain unit comprising the amino acid sequence of SEQ ID NO: 5, wherein the single-chain unit has specificity to CD3.
6. The method of claim 5 , wherein the tumor cell membrane surface antigen is selected from the group consisting of HER2, CD20, CD30 and CD133.