Human monoclonal antibodies specific for CD22
Disclosed herein are isolated human monoclonal antibodies that specifically bind human CD22 with a dissociation constant (K d ) of 25 nM or less. Nucleic acids encoding these antibodies, expression vectors including these nucleic acid molecules, and isolated host cells that express the nucleic acid molecules are also disclosed. The antibodies can be used to detect human CD22 in a sample. In some cases, CD22 is soluble CD22. Methods of diagnosing a B-cell malignancy, or confirming a B-cell malignancy diagnosis, are disclosed herein that utilize these antibodies. Methods of treating a subject with a B-cell malignancy are also disclosed.
1. A monoclonal antibody that specifically binds human CD22, the antibody comprising
a heavy chain or portion thereof, which comprises an amino acid sequence comprising residues 26-35 of SEQ ID NO: 3, residues 53-61 of SEQ ID NO: 3 and residues 100-113 of SEQ ID NO: 3, and
a light chain or portion thereof, which comprises an amino acid sequence comprising residues 27-32 of SEQ ID NO: 4, residues 50-52 of SEQ ID NO: 4 and residues 89-97 of SEQ ID NO: 4.
2. The monoclonal antibody of claim 1 , wherein the heavy chain or portion thereof comprises a variable heavy (V H ) region having the amino acid sequence of a VH region sequence present within SEQ ID NO: 3, or the light chain or portion thereof comprises a variable light (V L ) region having the amino acid sequence of a VL region sequence present within SEQ ID NO: 4, or both.
3. The monoclonal antibody of claim 1 , wherein the antibody comprises an Fab, an scFv or an IgG antibody.
4. A composition comprising the monoclonal antibody of claim 1 in a pharmaceutically acceptable carrier.
5. An immunoconjugate comprising the monoclonal antibody of claim 1 and an effector molecule.
6. The immunoconjugate of claim 5 , wherein the effector molecule comprises a toxin or a detectable label.
7. The immunoconjugate of claim 6 , wherein the effector molecule comprises the toxin, which comprises a Pseudomonas exotoxin.
8. The immunoconjugate of claim 6 , wherein the effector molecule comprises the detectable label, which comprises a fluorescent, enzymatic, or radioactive label.
9. A composition comprising the immunoconjugate of claim 5 in a pharmaceutically acceptable carrier.
10. A nucleic acid molecule encoding the monoclonal antibody of claim 1 .
11. The isolated nucleic acid molecule of claim 10 , which comprises (a) the nucleotide sequence of SEQ ID NO: 9 or a portion thereof encoding a heavy chain variable region and (b) the nucleotide sequence of SEQ ID NO: 10 or a portion thereof encoding a light chain variable region.
12. An expression vector comprising the nucleic acid molecule of claim 10 .
13. A host cell transformed with the nucleic acid molecule of claim 10 .
14. The monoclonal antibody of claim 1 , wherein the antibody binds to a human CD22 with a binding affinity of 20 nM or less.
15. The monoclonal antibody of claim 1 , wherein the heavy chain of the antibody comprises a V H region having at least 90% identity to a V H region present in the heavy chain sequence set forth in SEQ ID NO: 3, or the light chain of the antibody comprises a V L region having at least 90% identity to a V L region present in the light chain sequence set forth in SEQ ID NO: 4, or both.
16. The monoclonal antibody of claim 1 , wherein the heavy chain of the antibody comprises the amino acid sequence set forth in SEQ ID NO: 3, the light chain of the antibody comprises the amino acid sequence set forth in SEQ ID NO: 4, or both.
17. The monoclonal antibody of claim 1 , wherein the antibody is a human antibody.
18. A chimeric molecule comprising the monoclonal antibody of claim 1 and an effector molecule.
19. The chimeric molecule of claim 18 , wherein the antibody and effector molecule are present in a contiguous polypeptide, which is comprised by the chimeric molecule.
20. The chimeric molecule of claim 18 , wherein the effector molecule and antibody are joined via a covalent bond, or the chimeric molecule further comprises a peptide linker, or both.
21. A nucleic acid molecule encoding the chimeric molecule of claim 18 .
22. An expression vector comprising the nucleic acid molecule of claim 21 .
23. A host cell transformed with the nucleic acid molecule of claim 21 .