NZ767837B2

NZ767837B2 - Neutralization of inhibitory pathways in lymphocytes

Info

Publication number: NZ767837B2
Application number: NZ767837A
Authority: NZ
Inventors: Pascale Andre; Mathieu Blery; Carine Paturel; Nicolai Wagtmann
Original assignee: Innate Pharma
Filing date: 2015-09-15
Publication date: 2025-01-07

Abstract

The present invention relates to a combination therapy for the treatment of cancer, comprising an antibody that neutralizes the inhibitory activity of human natural killer cell lectin-like receptor C1 and an antibody that neutralizes the inhibitory activity of human programmed cell death 1 (PD-1) which is selected from pembrolizumab, nivolumab, AMP-514, MEDI-4736, CT-011 and MPDL3280A.

Claims

1. Use of an antibody that neutralizes the inhibitory activity of human natural killer cell lectin-like receptor C1 (NKG2A) comprising a heavy chain represented by any one of SEQ ID NOs: 4-8 and a light chain represented by SEQ ID NO: 9 in the manufacture of a medicament for treating a major histocompatibility complex IE (HLA-E) -expressing cancer, wherein the ment is to be administered with an antibody that neutralizes the inhibitory activity of human programmed cell death 1 (PD-1) selected from the group consisting of pembrolizumab, nivolumab, AMP-514, MEDI-4736, CT-011 and MPDL3280A.

2. The use of claim 1, wherein the the antibody that neutralizes the inhibitory activity of human NKG2A comprises a heavy chain represented by SEQ ID NO: 5 and a light chain represented by SEQ ID NO: 9.

3. The use of claim 1 or claim 2, wherein the antibody that neutralizes the inhibitory ty of human PD-1 is MEDI-4736.

4. The use of any one of claims 1-3, wherein the medicament is to be administered in at least two doses in an amount effective to achieve a continuous blood concentration of the antibody that neutralizes the tory activity of human NKG2A of at least 10 µg/ml for at least one week following administration thereof.

5. The use of any one of claims 1-4, wherein the medicament is to be stered in at least one administration cycle, wherein for each administration cycle, two, three or four doses of the medicament are to be stered and two, three or four doses of the dy that neutralizes the inhibitory activity of human PD-1 are to be administered.

6. The use of claim 5, wherein the stration cycle is a period of eight weeks.

7. The use of any one of claims 1-6, wherein the medicament and the antibody that neutralizes the inhibitory activity of human PD-1 are to be administered separately and sequentially.

8. The use of any one of claims 1-6, wherein the medicament and the antibody that neutralizes the inhibitory activity of human PD-1 are to be stered simultaneously on the same day.

9. Use of an antibody that neutralizes the inhibitory activity of human NKG2A sing a heavy chain represented by any one of SEQ ID NOs: 4-8 and a light chain represented by SEQ ID NO: 9, and an antibody that neutralizes the inhibitory activity of human PD-1 in the manufacture of a medicament for treating an expressing cancer, and wherein the antibody that neutralizes the inhibitory activity of human PD-1 is selected from the group consisting of pembrolizumab, nivolumab, 4, MEDI-4736, CT-011 and MPDL3280A.

10. The use of any one of claims 1-9, n the HLA-E-expressing cancer is a solid tumor.

11. The use of any one of claims 1-9, wherein the HLA-E-expressing cancer is hematological tumor.

12. The use of any one of claims 1-9, wherein the expressing cancer is selected from the group consisting of lung cancer, renal cell carcinoma (RCC), melanoma, colorectal cancer, and ovarian cancer.

13. The use of claim 12, wherein the lung cancer is non-small cell lung cancer.

14. The use of claim 13, wherein the non-small cell lung cancer is an advanced cancer.

15. The use of claim 13 or claim 14, wherein the non-small cell lung cancer is a refractory cancer.

16. A pharmaceutical composition comprising an antibody that lizes the inhibitory activity of human NKG2A, an antibody that neutralizes the tory activity of human PD-1, and a pharmaceutically acceptable carrier, wherein the antibody that neutralizes the tory activity of human NKG2A comprises a heavy chain represented by any one of SEQ ID NOs: 4-8 and a light chain represented by SEQ ID NO: 9, and wherein the antibody that neutralizes the inhibitory activity of human PD-1 is selected from the group consisting of pembrolizumab, nivolumab, AMP-514, MEDI-4736, CT-011 and MPDL3280A.

17. The pharmaceutical composition of claim 16, wherein the antibody that neutralizes the inhibitory activity of human NKG2A comprises a heavy chain represented by SEQ ID NO: 5 and a light chain represented by SEQ ID NO: 9.

18. The pharmaceutical composition of claim 16 or claim 17, wherein the dy that neutralizes the inhibitory activity of human PD-1 is MEDI-4736.

19. A kit sing: (a) a dose of an dy that lizes the inhibitory activity of human NKG2A, and (b) a dose of an antibody that neutralizes the inhibitory activity of human PD-1, wherein the antibody that neutralizes the inhibitory activity of human NKG2A comprises a heavy chain represented by any one of SEQ ID NOs: 4-8 and a light chain represented by SEQ ID NO: 9, and wherein the antibody that neutralizes the inhibitory activity of human PD-1 is selected from the group consisting of pembrolizumab, nivolumab, AMP-514, MEDI-4736, CT-011 and MPDL3280A.

20. The kit of claim 19, wherein the dy that neutralizes the inhibitory activity of human NKG2A ses a heavy chain represented by SEQ ID NO: 5 and a light chain represented by SEQ ID NO: 9.

21. The kit of claim 19 or claim 20, wherein the dy that neutralizes the inhibitory activity of human PD-1 is MEDI-4736.

22. The kit of any one of claims 19-21, n the kit comprises: (a) multiple packages of single-dose pharmaceutical compositions containing an effective amount of the antibody that neutralizes the inhibitory activity of human NKG2A, and (b) multiple packages of single-dose pharmaceutical compositions containing an effective amount of the antibody that neutralizes the tory activity of human PD-1.