Humanized anti-CD70 binding agents and uses thereof
Disclosed are CD70 binding agents, such as humanized anti-CD70 antibodies and fragments and derivatives, that exert a cytotoxic, cytostatic or immunomodulatory on CD70 expressing cells, as well as pharmaceutical compositions and kits comprising the antibody, fragment or derivative. Also disclosed are methods for the treatment of CD70-expressing cancers and immunological disorders, comprising administering to a subject the CD70 binding agents or pharmaceutical compositions.
1. An isolated polynucleotide encoding a humanized heavy chain variable region comprising the amino acid sequence of SEQ ID NO:14, and encoding a humanized light chain variable region comprising the amino acid sequence of SEQ ID NO:24.
2. The isolated polynucleotide of claim 1 , comprising the nucleotide sequence of SEQ ID NO:13 and the nucleotide sequence of SEQ ID NO:23.
3. The isolated polynucleotide of claim 1 , further encoding a human IgG constant region.
4. The isolated polynucleotide of claim 3 , wherein the IgG constant region is IgG1 or IgG3.
5. The isolated polynucleotide of claim 3 , further encoding a human kappa constant region.
6. The isolated polynucleotide of claim 5 , wherein the humanized heavy chain variable region and the human IgG constant region together comprise the amino acid sequence corresponding to residues 20-467 of SEQ ID NO:16 and the humanized light chain variable region and the human kappa constant region together comprise the amino acid sequence corresponding to residues 21-238 of SEQ ID NO:26.
7. The isolated polynucleotide of claim 6 , comprising the nucleotide sequence of nucleotides 58-1401 of SEQ ID NO:15 and the nucleotide sequence of nucleotides 61-714 of SEQ ID NO:25.
8. A pair of isolated polynucleotides comprising a first polynucleotide encoding a humanized heavy chain variable region comprising the amino acid sequence of SEQ ID NO:14, and a second polynucleotide encoding a humanized light chain variable region comprising the amino acid sequence of SEQ ID NO:24.
9. The pair of isolated polynucleotides of claim 8 , wherein the first polynucleotide comprises the nucleotide sequence of SEQ ID NO:13 and the second polynucleotide comprises the nucleotide sequence of SEQ ID NO:23.
10. The pair of isolated polynucleotides of claim 8 , wherein the first polynucleotide further encodes a human IgG constant region.
11. The pair of isolated polynucleotides of claim 10 , wherein the IgG constant region is IgG1 or IgG3.
12. The pair of isolated polynucleotides of claim 10 , wherein the second polynucleotide further encodes a human kappa constant region.
13. The pair of isolated polynucleotides of claim 12 , wherein the humanized heavy chain variable region and the human IgG constant region together comprise the amino acid sequence corresponding to residues 20-467 of SEQ ID NO:16 and the humanized light chain variable region and the human kappa constant region together comprise the amino acid sequence corresponding to residues 21-238 of SEQ ID NO:26.
14. The pair of isolated polynucleotides of claim 13 , wherein the first polynucleotide comprises the nucleotide sequence of nucleotides 58-1401 of SEQ ID NO:15 and the second polynucleotide comprises the nucleotide sequence of nucleotides 61-714 of SEQ ID NO:25.
15. A vector comprising the isolated polynucleotide of claim 1 .
16. A vector or vectors comprising the pair of isolated polynucleotides of claim 8 .
17. The vector or vectors of claim 16 , wherein a first vector comprises the first polynucleotide and a second vector comprises the second polynucleotide.
18. A host cell transfected with the vector of claim 15 .
19. A host cell transfected with the vector or vectors of claim 16 .
20. The host cell of claim 18 that is a mammalian host cell.
21. The host cell of claim 20 , wherein the mammalian host cell is selected from the group consisting of CHO, VERO, BHK, HeLa, COS, MDCK, 293, 3T3, and W138 cells.
22. The host cell of claim 19 that is a mammalian host cell.
23. The host cell of claim 22 , wherein the mammalian host cell is selected from the group consisting of CHO, VERO, BHK, HeLa, COS, MDCK, 293, 3T3, and W138 cells.
24. A method of producing an antibody, comprising culturing the host cell of claim 18 to produce the antibody.
25. A method of producing an antibody, comprising culturing the host cell of claim 19 to produce the antibody.