Antibody conjugates and methods of making and using the same
Antibodies that include a sulfatase motif-containing tag in a constant region of an immunoglobulin (Ig) light chain polypeptide are disclosed. The sulfatase motif can be converted by a formylglycine-generating enzyme (FGE) to produce a formylglycine (fGly)-modified Ig light chain polypeptide. An fGly-modified Ig light chain polypeptide of the antibody can be covalently and site-specifically bound to a moiety of interest to provide an antibody conjugate. The disclosure also encompasses methods of production of such tagged Ig light chain polypeptides, fGly-modified Ig light chain polypeptides, and antibody conjugates, as well as methods of use of same.
1. An antibody comprising an immunoglobulin (Ig) kappa light chain polypeptide comprising, in a constant region, an amino acid sequence selected from
the group consisting of: SEQ ID NO: 2, SEQ ID NO: 4, SEQ ID NO: 17, SEQ ID NO: 18, SEQ ID NO: 26, SEQ ID NO: 28, SEQ ID NO: 31, SEQ ID NO: 37, SEQ ID NO: 44, and SEQ ID NO: 45.
2. The antibody of claim 1 , wherein the Ig kappa light chain polypeptide comprises, in the constant region, the amino acid sequence of SEQ ID NO: 2.
3. The antibody of claim 1 , wherein the Ig kappa light chain polypeptide comprises, in the constant region, the amino acid sequence of SEQ ID NO: 4.
4. The antibody of claim 1 , wherein the Ig kappa light chain polypeptide comprises, in the constant region, the amino acid sequence of SEQ ID NO: 17.
5. The antibody of claim 1 , wherein the Ig kappa light chain polypeptide comprises, in the constant region, the amino acid sequence of SEQ ID NO: 18.
6. The antibody of claim 1 , wherein the Ig kappa light chain polypeptide comprises, in the constant region, the amino acid sequence of SEQ ID NO: 26.
7. The antibody of claim 1 , wherein the Ig kappa light chain polypeptide comprises, in the constant region, the amino acid sequence of SEQ ID NO: 28.
8. The antibody of claim 1 , wherein the Ig kappa light chain polypeptide comprises, in the constant region, the amino acid sequence of SEQ ID NO: 31.
9. The antibody of claim 1 , wherein the Ig kappa light chain polypeptide comprises, in the constant region, the amino acid sequence of SEQ ID NO: 37.
10. The antibody of claim 1 , wherein the Ig kappa light chain polypeptide comprises, in the constant region, the amino acid sequence of SEQ ID NO: 44.
11. The antibody of claim 1 , wherein the Ig kappa light chain polypeptide comprises, in the constant region, the amino acid sequence of SEQ ID NO: 45.
12. The antibody of claim 1 , wherein the antibody specifically binds a tumor antigen on a cancer cell.
13. A recombinant nucleic acid comprising a nucleotide sequence encoding the Ig kappa light chain polypeptide of the antibody of claim 1 .
14. A recombinant expression vector comprising the nucleic acid of claim 13 , wherein the Ig kappa light chain polypeptide-encoding nucleotide sequence is operably linked to a promoter.
15. A recombinant expression vector comprising a nucleotide sequence encoding an Ig heavy chain polypeptide of the antibody of claim 1 .
16. A host cell genetically modified to express the antibody of claim 1 .
17. The host cell of claim 16 , genetically modified to express a formylglycine generating enzyme (FGE), in a manner sufficient to convert the Ig kappa light chain polypeptide into an fGly-modified Ig kappa light chain polypeptide.
18. The host cell of claim 16 , wherein the host cell is a mammalian cell.
19. A formulation comprising: the antibody of claim 1 and a pharmaceutically acceptable excipient.