Folate receptor 1 antibodies and immunoconjugates and uses thereof
Novel anti-cancer agents, including, but not limited to, antibodies and immunoconjugates, that bind to human folate receptor 1 are provided. Methods of using the agents, antibodies, or immunoconjugates, such as methods of inhibiting tumor growth are further provided.
1. An isolated polynucleotide comprising the nucleotide sequence of SEQ ID NO:5,
wherein the polynucleotide encodes a heavy chain (HC) variable domain of an antibody or antigen binding fragment thereof that specifically binds human folate receptor 1.
2. The isolated polynucleotide of claim 1 , wherein the polynucleotide further comprises the nucleotide sequence of SEQ ID NO: 14 or SEQ ID NO: 15.
3. A vector comprising the polynucleotide of claim 1 .
4. A vector comprising the polynucleotide of claim 1 .
5. An isolated host cell comprising the polynucleotide of claim 1 .
6. An isolated host cell comprising the polynucleotide of claim 2 .
7. An isolated polynucleotide comprising the nucleotide sequence of SEQ ID NO:14 or SEQ ID NO:15,
wherein the polynucleotide encodes a light chain (LC) variable domain of an antibody or antigen binding fragment thereof that specifically binds human folate receptor 1.
8. The isolated polynucleotide of claim 7 , wherein the polynucleotide comprises the nucleotide sequence of SEQ ID NO: 14.
9. The isolated polynucleotide of claim 7 , wherein the polynucleotide comprises the nucleotide sequence of SEQ ID NO: 15.
10. A vector comprising the polynucleotide of claim 8 .
11. A vector comprising the polynucleotide of claim 9 .
12. An isolated host cell comprising the polynucleotide of claim 8 .
13. An isolated host cell comprising the polynucleotide of claim 9 .
14. An isolated polynucleotide encoding a polypeptide comprising an HC variable domain of an antibody or antigen binding fragment thereof that specifically binds human folate receptor 1, wherein the antibody or antigen binding fragment thereof comprises:
(1) the HC variable domain comprising (a) a HC CDR1 comprising the amino acid sequence of GYFMN (SEQ ID NO: 1); (b) a HC CDR2 comprising the amino acid sequence of RIHPYDGDTFYNQKFQG (SEQ ID NO: 2); and (c) a HC CDR3 comprising the amino acid sequence of YDGSRAMDY (SEQ ID NO:3), and
(2) a LC variable domain comprising (a) a LC CDR1 comprising the amino acid sequence of KASQSVSFAGTSLMH (SEQ ID NO:7); (b) a LC CDR2 comprising the amino acid sequence of RASNLEA (SEQ ID NO:8); and (c) a LC CDR3 comprising the amino acid sequence of QQSREYPYT (SEQ ID NO:9).
15. The isolated polynucleotide of claim 14 , wherein the HC variable domain comprises the amino acid sequence of SEQ ID NO:4.
16. The isolated polynucleotide of claim 15 , wherein the polynucleotide encodes a HC comprising the amino acid sequence of SEQ ID NO:6.
17. The isolated polynucleotide of claim 14 , wherein the polynucleotide further encodes a polypeptide comprising the LC variable domain, wherein the LC variable domain comprises: (a) a LC CDR1 comprising the amino acid sequence of KASQSVSFAGTSLMH (SEQ ID NO:7); (b) a LC CDR2 comprising the amino acid sequence of RASNLEA (SEQ ID NO:8); and (c) a LC CDR3 comprising the amino acid sequence of QQSREYPYT (SEQ ID NO:9).
18. The isolated polynucleotide of claim 17 , wherein the LC variable domain comprises the amino acid sequence of SEQ ID NO: 10.
19. The isolated polynucleotide of claim 18 , wherein the polynucleotide encodes a LC comprising the amino acid sequence of SEQ ID NO: 12.
20. The isolated polynucleotide of claim 17 , wherein the LC variable domain comprises the amino acid sequence of SEQ ID NO: 11.
21. The isolated polynucleotide of claim 20 , wherein the polynucleotide encodes a LC comprising the amino acid sequence of SEQ ID NO: 13.
22. The isolated polynucleotide of claim 17 , wherein the HC variable domain comprises the amino acid sequence of SEQ ID NO:4, and wherein the LC variable domain comprises the amino acid sequence of SEQ ID NO: 10.
23. The isolated polynucleotide of claim 22 , wherein the polynucleotide encodes a HC comprising the amino acid sequence of SEQ ID NO:6, and wherein the polynucleotide encodes a LC comprising the amino acid sequence of SEQ ID NO: 12.
24. The isolated polynucleotide of claim 17 , wherein the HC variable domain comprises the amino acid sequence of SEQ ID NO:4, and wherein the LC variable domain comprises the amino acid sequence of SEQ ID NO: 11.
25. The isolated polynucleotide of claim 24 , wherein the polynucleotide encodes a HC comprising the amino acid sequence of SEQ ID NO:6, and wherein the polynucleotide encodes a LC comprising the amino acid sequence of SEQ ID NO: 13.
26. A vector comprising the polynucleotide of claim 14 .
27. A vector comprising the polynucleotide of claim 17 .
28. An isolated host cell comprising the polynucleotide of claim 14 .
29. An isolated host cell comprising the polynucleotide of claim 17 .
30. The isolated polynucleotide of claim 1 , wherein the HC of the antibody comprises the amino acid sequence of SEQ ID NO:6, and wherein the LC of the antibody comprises the amino acid sequence of SEQ ID NO: 12 or 13.
31. The isolated polynucleotide of claim 1 , wherein the HC of the antibody comprises the same amino acid sequence as the amino acid sequence of the heavy chain encoded by the plasmid deposited with the American Type Culture Collection (ATCC) as PTA-10772, and wherein the LC of the antibody comprises the same amino acid sequence as the amino acid sequence of the light chain encoded by the plasmid deposited with the ATCC as PTA-10773 or PTA-10774.
32. The isolated polynucleotide of claim 7 , wherein the HC of the antibody comprises the amino acid sequence of SEQ ID NO:6, and wherein the LC of the antibody comprises the amino acid sequence of SEQ ID NO: 12 or 13.
33. The isolated polynucleotide of claim 7 , wherein the HC of the antibody comprises the same amino acid sequence as the amino acid sequence of the heavy chain encoded by the plasmid deposited with the ATCC as PTA-10772, and wherein the LC of the antibody comprises the same amino acid sequence as the amino acid sequence of the light chain encoded by the plasmid deposited with the ATCC as PTA-10773 or PTA-10774.
34. The isolated polynucleotide of claim 14 , wherein the LC of the antibody comprises the amino acid sequence of SEQ ID NO: 12 or 13.
35. The isolated polynucleotide of claim 14 , wherein the LC of the antibody comprises the same amino acid sequence as the amino acid sequence of the light chain encoded by the plasmid deposited with the ATCC as PTA-10773 or PTA-10774.
36. The isolated polynucleotide of claim 15 , wherein the polynucleotide encodes a HC comprising the same amino acid sequence as the amino acid sequence of the heavy chain encoded by the plasmid deposited with the ATCC as PTA-10772.
37. The isolated polynucleotide of claim 18 , wherein the polynucleotide encodes a LC comprising the same amino acid sequence as the amino acid sequence of the light chain encoded by the plasmid deposited with the ATCC as PTA-10773.
38. The isolated polynucleotide of claim 20 , wherein the polynucleotide encodes a LC comprising the same amino acid sequence as the amino acid sequence of the light chain encoded by the plasmid deposited with the ATCC as PTA-10774.
39. The isolated polynucleotide of claim 22 , wherein the polynucleotide encodes a HC comprising the same amino acid sequence as the amino acid sequence of the heavy chain encoded by the plasmid deposited with the ATCC as PTA-10772, and wherein the polynucleotide encodes a LC comprising the same amino acid sequence as the amino acid sequence of the light chain encoded by the plasmid deposited with the ATCC as PTA-10773.
40. The isolated polynucleotide of claim 24 , wherein the polynucleotide encodes a HC comprising the same amino acid sequence as the amino acid sequence of the heavy chain encoded by the plasmid deposited with the ATCC as PTA-10772, and wherein the polynucleotide encodes a LC comprising the same amino acid sequence as the amino acid sequence of the light chain encoded by the plasmid deposited with the ATCC as PTA-10774.