Bispecific antibody for cancer immunotherapy
View Patent ↗Disclosed are compositions and methods for targeted treatment of TAG-72-expressing cancers. In particular, bispecific antibodies are disclosed that are able to engage T-cells to destroy TAG-72-expressing malignant cells.
1. A bispecific antibody comprising
an anti-TAG72 single chain variable fragment (scFv) antibody that specifically binds human TAG72 linked to an anti-CD3 scFv that specifically binds human CD3 epsilon subunit;
wherein the anti-TAG72 scFv comprises a variable heavy (V H ) domain and a variable light (V L ) domain separated by a peptide linker comprising the amino acid sequence of SEQ ID NO:5;
wherein the V H domain comprises CDR1, CDR2 and CDR3 domains having the amino acid sequences of SEQ ID NOs: 12, 13 and 14, respectively; and
wherein the V L domain comprises CDR1, CDR2 and CDR3 domains having the amino acid sequences of SEQ ID NOs: 15, 16 and 17, respectively.
2. The bispecific antibody of claim 1 , wherein the anti-CD3 scFv comprises the amino acid sequence of SEQ ID NO:19.
3. The bispecific antibody of claim 1 , wherein the anti-TAG72 V H domain comprises the amino acid sequence of SEQ ID NO: 2.
4. The bispecific antibody of claim 1 , wherein the anti-TAG72 V L domain comprises the amino acid sequence of SEQ ID NO:4.
5. The bispecific antibody of claim 1 , wherein the antibody comprises the amino acid sequence of SEQ ID NO: 11.
6. A pharmaceutical composition comprising the bispecific antibody of claim 1 in a pharmaceutically acceptable carrier.
7. An isolated nucleic acid encoding the bispecific antibody of claim 1 .
8. A method for treating a TAG72 expressing breast or ovarian cancer in a subject in need thereof, comprising administering to the subject a therapeutically effective amount of the pharmaceutical composition of claim 6 , wherein the anti-CD3 scFv comprises the amino acid sequence of SEQ ID NO:19.