Anti-CCR8 antibodies and uses thereof
The present invention provides anti-CCR8 antibodies and antigen-binding fragments thereof, and methods of making and using said anti-CCR8 antibodies and antigen-binding fragments thereof.
1. An antibody that binds to human C—C chemokine receptor type 8 (CCR8), the antibody comprising:
(a) a heavy chain complementarity-determining region (HCDR) 1 amino acid sequence comprising SEQ ID NO: 839;
(b) an HCDR2 amino acid sequence comprising SEQ ID NO: 840,
(c) an HCDR3 amino acid sequence comprising SEQ ID NO: 841,
(d) a light chain complementarity-determining region (LCDR) 1 amino acid sequence comprising SEQ ID NO: 842,
(e) an LCDR2 amino acid sequence comprising SEQ ID NO: 843, and
(f) an LCDR3 amino acid sequence comprising SEQ ID NO: 844.
2. The antibody of claim 1 , the antibody comprising:
a heavy chain variable region (HCVR) amino acid sequence of comprising SEQ ID NO: 1017, and
a light chain variable region (LCVR) comprising the amino acid sequence: DIVMTQSPDSLAVSLGERATINCKSSQSVLYSSNNXINYLAWYX 2 QKPGQX 3 PKLLIS WASTRESGVPDRFSGSGSGTDFTLTINSLQAEDVAVYYCQQYYSIPITFGGGTKVEIK R (SEQ ID NO: 1236),
wherein X 1 is R, X 2 is H or Q, and X 3 is S or P.
3. The antibody of claim 1 , the antibody comprising:
a HCVR amino acid sequence of SEQ ID NO: 1017, and
a LCVR amino acid sequence of SEQ ID NO: 1018.
4. A pharmaceutical composition comprising the antibody of claim 3 and a pharmaceutically acceptable carrier.
5. The antibody of claim 1 , the antibody comprising:
a heavy chain (HC) amino acid sequence comprising SEQ ID NO: 1125, and
a light chain (LC) amino acid sequence comprising SEQ ID NO: 1126.
6. The antibody of claim 1 , which is an afucosylated antibody.
7. A pharmaceutical composition comprising the antibody of claim 1 and a pharmaceutically acceptable carrier.
8. A method of inhibiting further progression of cancer in a patient, comprising administering an effective amount of a pharmaceutical composition comprising the antibody of claim 1 to the patient,
wherein the cancer is non-small cell lung cancer, gastric cancer, head and neck squamous cell carcinoma, hepatocellular carcinoma, triple-negative breast cancer, colorectal cancer, pancreatic cancer, or metastatic castrate-resistant prostate cancer.
9. The method of claim 8 , which further comprises administering an effective amount of a PD-1 antagonist antibody to the patient, wherein said PD-1 antagonist binds to PD-1 and decreases or blocks signal transduction resulting from the interaction of PD-1 and one or more of its ligands.
10. The method of claim 8 , wherein the cancer is non-small cell lung cancer.
11. An antibody that binds to human C—C chemokine receptor type 8 (CCR8), wherein said antibody is obtained by a process comprising cultivating a mammalian cell comprising a vector comprising:
a nucleic acid sequence encoding a heavy chain (HC) comprising an HCDR1 amino acid sequence comprising SEQ ID NO: 839, an HCDR2 amino acid sequence comprising SEQ ID NO: 840, and an HCDR3 amino acid sequence comprising SEQ ID NO: 841, and
a nucleic acid sequence encoding a light chain (LC) comprising an LCDR1 amino acid sequence comprising SEQ ID NO: 842, an LCDR2 amino acid sequence comprising SEQ ID NO: 843, and an LCDR3 amino acid sequence comprising SEQ ID NO: 844,
under conditions such that the antibody is expressed and recovering the expressed antibody.
12. The antibody of claim 11 , wherein said antibody is obtained by a process comprising cultivating a mammalian cell comprising a vector comprising:
a nucleic acid sequence encoding a HCVR amino acid sequence at least 90% identical to SEQ ID NO: 1017, and
a nucleic acid sequence encoding a LCVR amino acid sequence at least 90% identical to SEQ ID NO: 1018,
under conditions such that the antibody is expressed and recovering the expressed antibody.
13. The antibody of claim 11 , wherein said antibody is obtained by a process comprising cultivating a mammalian cell comprising a vector comprising:
a nucleic acid sequence encoding a HCVR amino acid sequence comprising SEQ ID NO: 1017, and
a nucleic acid sequence encoding a LCVR amino acid sequence comprising SEQ ID NO: 1018,
under conditions such that the antibody is expressed and recovering the expressed antibody.
14. The antibody of claim 11 , wherein said antibody is obtained by a process comprising cultivating a mammalian cell comprising a vector comprising:
a nucleic acid sequence encoding a HC amino acid sequence at least 90% identical to SEQ ID NO: 1125 or SEQ ID NO: 1237, and
a nucleic acid sequence encoding a LC amino acid sequence at least 90% identical to SEQ ID NO: 1126,
under conditions such that the antibody is expressed and recovering the expressed antibody.
15. The antibody of claim 11 , wherein said antibody is obtained by a process comprising cultivating a mammalian cell comprising a vector comprising:
a nucleic acid sequence encoding a HC amino acid sequence comprising SEQ ID NO: 1125 or SEQ ID NO: 1237, and
nucleic acid sequence encoding a LC amino acid sequence comprising SEQ ID NO: 1126,
under conditions such that the antibody is expressed and recovering the expressed antibody.
16. An antibody that binds to human C—C chemokine receptor type 8 (CCR8), wherein said antibody is obtained by a process comprising cultivating a mammalian cell comprising: a vector comprising a nucleic acid sequence encoding an HCR1 amino acid sequence comprising SEQ ID NO: 839, an HCR2 amino acid sequence comprising
SEQ ID NO: 840, and an HCDR3 amino acid sequence comprising SEQ ID NO: 841, and a vector comprising a nucleic acid sequence encoding an LCDR1 amino acid sequence comprising SEQ ID NO: 842, an LCDR2 amino acid sequence comprising SEQ ID NO: 843, and an LCDR3 amino acid sequence comprising SEQ ID NO: 844, under conditions such that the antibody is expressed and recovering the expressed antibody.
17. A single chain variable fragment (scFv), Fab, or single chain Fab (scFab) that binds to human C—C chemokine receptor type 8 (CCR8), wherein said scFv, Fab, or scFab comprises:
(a) an HCDR1 amino acid sequence comprising SEQ ID NO: 839;
(b) an HCDR2 amino acid sequence comprising SEQ ID NO: 840,
(c) an HCDR3 amino acid sequence comprising SEQ ID NO: 841,
(d) an LCDR1 amino acid sequence comprising SEQ ID NO: 842,
(e) an LCDR2 amino acid sequence comprising SEQ ID NO: 843, and
(f) an LCDR3 amino acid sequence comprising SEQ ID NO: 844.
18. The scFv, Fab, or scFab of claim 17 , the scFv, Fab, or scFab comprising:
a heavy chain variable region (HCVR) amino acid sequence comprising SEQ ID NO: 1017, and
a light chain variable region (LCVR) comprising the amino acid sequence: DIVMTQSPDSLAVSLGERATINCKSSQSVLYSSNNXINYLAWYX 2 QKPGQX 3 P KLLISWASTRESGVPDRFSGSGSGTDFTLTINSLQAEDVAVYYCQQYYSIPITF GGGTKVEIKR (SEQ ID NO: 1236),
wherein X 1 is R, X 2 is H or Q, and X 3 is S or P.
19. The scFv, Fab, or scFab of claim 17 , the scFv, Fab, or scFab comprising:
a LCVR comprising the amino acid sequence comprising SEQ ID NO: 1018, and
a HCVR amino acid sequence comprising SEQ ID NO: 1017.
20. An antibody that binds to human C—C chemokine receptor type 8 (CCR8), the antibody comprising:
a heavy chain (HC) amino acid sequence comprising SEQ ID NO: 1237, and
a light chain (LC) amino acid sequence comprising SEQ ID NO: 1126.
21. A pharmaceutical composition comprising the antibody of claim 20 and a pharmaceutically acceptable carrier.
22. An antibody that binds to human C—C chemokine receptor type 8 (CCR8), the antibody comprising:
(a) an HCDR1 amino acid sequence comprising SEQ ID NO: 839;
(b) an HCDR2 amino acid sequence comprising SEQ ID NO: 840,
(c) an HCDR3 amino acid sequence comprising SEQ ID NO: 841,
(d) an LCDR1 amino acid sequence comprising SEQ ID NO: 950,
(e) an LCDR2 amino acid sequence comprising SEQ ID NO: 843, and
(f) an LCDR3 amino acid sequence comprising SEQ ID NO: 844.
23. The antibody of claim 22 , wherein said antibody comprises:
an HCVR amino acid sequence of SEQ ID NO: 1017, and
an LCVR amino acid sequence of SEQ ID NO: 353.
24. The antibody of claim 22 , comprising:
a HC amino acid sequence comprising SEQ ID NO: 1125 or SEQ ID NO: 1237, and
a LC amino acid sequence of SEQ ID NO: 355.
25. The antibody of claim 22 , comprising:
a HC amino acid sequence comprising SEQ ID NO: 1237, and
a LC amino acid sequence of SEQ ID NO: 355.
26. The antibody of claim 22 , comprising:
a HC amino acid sequence comprising SEQ ID NO: 1125, and
a LC amino acid sequence comprising SEQ ID NO: 355.
27. An antibody that binds to human C—C chemokine receptor type 8 (CCR8), the antibody comprising:
(a) a heavy chain complementarity-determining region (HCDR) 1 amino acid sequence consisting of SEQ ID NO: 839;
(b) an HCDR2 amino acid sequence consisting of SEQ ID NO: 840,
(c) an HCDR3 amino acid sequence consisting of SEQ ID NO: 841,
(d) a light chain complementarity-determining region (LCDR) 1 amino acid sequence consisting of SEQ ID NO: 842,
(e) an LCDR2 amino acid sequence consisting of SEQ ID NO: 843, and
(f) an LCDR3 amino acid sequence consisting of SEQ ID NO: 844.
28. The antibody of claim 27 , the antibody comprising:
a heavy chain (HC) amino acid sequence consisting of SEQ ID NO: 1237, and
a light chain (LC) amino acid sequence consisting of SEQ ID NO: 1126.
29. The antibody of claim 27 , the antibody comprising:
a HCVR amino acid sequence consisting of SEQ ID NO: 1017, and
a LCVR amino acid sequence consisting of SEQ ID NO: 1018.