Anti-ULBP6 antibodies
The present disclosure relates to a ULBP6 binding protein that inhibits the interaction between ULBP6 and NKG2D, and methods of treating cancer with said ULBP6 binding protein.
1. An anti-ULBP6 antibody comprising 6 CDRs selected from the following:
CDRH1 of SEQ ID NO: 36, CDRH2 of SEQ ID NO: 37, CDRH3 of SEQ ID NO: 38, CDRL1 of SEQ ID NO: 51, CDRL2 of SEQ ID NO: 52 and CDRL3 of SEQ ID NO: 53;
CDRH1 of SEQ ID NO: 39, CDRH2 of SEQ ID NO: 40, CDRH3 of SEQ ID NO: 41, CDRL1 of SEQ ID NO: 54, CDRL2 of SEQ ID NO: 55 and CDRL3 of SEQ ID NO: 56;
CDRH1 of SEQ ID NO: 42, CDRH2 of SEQ ID NO: 43, CDRH3 of SEQ ID NO: 44, CDRL1 of SEQ ID NO: 57, CDRL2 of SEQ ID NO: 58 and CDRL3 of SEQ ID NO: 59; or
CDRH1 of SEQ ID NO: 45, CDRH2 of SEQ ID NO: 46, CDRH3 of SEQ ID NO: 47, CDRL1 of SEQ ID NO: 60, CDRL2 of SEQ ID NO: 61 and CDRL3 of SEQ ID NO: 62.
2. The anti-ULBP6 antibody according to claim 1 , wherein the antibody comprises:
a VH region that is at least 80% identical to SEQ ID NO: 21 and a VL region that is at least 80% identical to SEQ ID NO: 31;
a VH region that is at least 80% identical to SEQ ID NO: 22 and a VL region that is at least 80% identical to SEQ ID NO: 32;
a VH region that is at least 80% identical to SEQ ID NO: 23 and a VL region that is at least 80% identical to SEQ ID NO: 33; or
a VH region that is at least 80% identical to SEQ ID NO: 24 and a VL region that is at least 80% identical to SEQ ID NO: 34.
3. The anti-ULBP6 antibody according to claim 1 , wherein the antibody comprises:
a) a Heavy Chain (HC) sequence at least 80% identical to any one of SEQ ID NOs: 75-78, 85-88 or 95-98; and/or
b) a Light Chain (LC) sequence at least 80% identical to any one of SEQ ID NOs: 105-108.
4. The anti-ULBP6 antibody according to claim 1 , wherein the antibody inhibits the interaction of human ULBP6 and human NKG2D.
5. The anti-ULBP6 antibody according to claim 1 , wherein the antibody inhibits the binding of soluble ULBP6 to NKG2D.
6. The anti-ULBP6 antibody according to claim 1 , wherein the antibody comprises a modified Fc region.
7. The anti-ULBP6 antibody according to claim 6 , wherein the modified Fc region comprises the amino acid substitutions S239D and 1332E (as numbered according to the EU index).
8. The anti-ULBP6 antibody according to claim 1 , wherein the antibody is afucosylated.
9. The anti-ULBP6 antibody according to claim 6 , wherein the modified Fc region comprises amino acid substitutions selected from S239D/A330L/1332E, G236A/S239D/A330L/1332E, L235V/F243L/R292P/Y300L/P396L or F243L/R292P/Y300L/V305l/P396L (as numbered according to the EU index).
10. An isolated nucleic acid which encodes an amino acid sequence of the anti-ULBP6 antibody of claim 1 .
11. An expression vector comprising the isolated nucleic acid of claim 10 .
12. A recombinant host cell comprising the isolated nucleic acid of claim 10 .
13. A recombinant host cell comprising the expression vector of claim 11 .
14. A method for the production of an anti-ULBP6 antibody comprising culturing a recombinant host cell of claim 12 under suitable conditions whereby the anti-ULBP6 antibody is produced.
15. A cell line that expresses the anti-ULBP6 antibody of claim 1 .
16. A pharmaceutical composition comprising the anti-ULBP6 antibody of claim 1 and a pharmaceutically acceptable excipient.
17. A method for the treatment of cancer in a subject in need thereof comprising administering to said subject a therapeutically effective amount of the anti-ULBP6 antibody of claim 1 .