Method of reducing tumor relapse rate in immunotherapy by administration of lenzilumab

1. A method for reducing relapse rate or preventing occurrence of tumor relapse in a subject treated with immunotherapy, the method comprising administering to the subject a recombinant hGM-CSF antagonist, wherein the recombinant hGM-CSF antagonist is anti-hGM-CSF antibody lenzilumab.

2. The method of claim 1 , wherein said immunotherapy comprises adoptive cell transfer, administration of monoclonal antibodies, administration of cytokines, administration of a cancer vaccine, T cell engaging therapies, or any combination thereof.

3. The method of claim 2 , wherein the adoptive cell transfer comprises administering chimeric antigen receptor-expressing T-cells (CAR T-cells), T-cell receptor (TCR) modified T-cells, tumor-infiltrating lymphocytes (TIL), chimeric antigen receptor (CAR)-modified natural killer cells, or dendritic cells, or any combination thereof.

4. The method of claim 1 , wherein the anti-hGM-CSF antibody lenzilumab binds a human GM-CSF.

5. The method of claim 1 , wherein the anti-hGM-CSF antibody lenzilumab binds a primate GM-CS F.

6. The method of claim 1 , wherein the anti-hGM-CSF antibody lenzilumab binds a mammalian GM-CSF.

7. The method of claim 1 , wherein the anti-hGM-CSF antibody lenzilumab is a monoclonal antibody.

8. The method of claim 1 , wherein the anti-hGM-CSF antibody lenzilumab is a human GM-CSF neutralizing antibody.

9. The method of claim 1 , wherein the anti-hGM-CSF antibody lenzilumab is a recombinant antibody.

10. The method of claim 1 , wherein the anti-hGM-CSF antibody lenzilumab is an engineered human antibody.

11. The method of claim 1 , wherein the anti-hGM-CSF antibody lenzilumab binds to the same epitope as chimeric 19/2.

12. The method of claim 1 , wherein the anti-hGM-CSF antibody lenzilumab comprises a VH region that comprises a CDR3 binding specificity determinant RQRFPY (SEQ ID NO: 12), a J segment, and a V-segment, wherein the J-segment comprises at least 95% identity to human JH4 (YFDYWGQGTLVTVSS) (SEQ ID NO: 14) and the V-segment comprises at least 90% identity to a human germ line VHl 1-03 sequence.

13. The method of claim 12 , wherein the J segment comprises YFDYWGQGTLVTVSS (SEQ ID NO: 14).

14. The method of claim 12 , wherein the CDR3 comprises RQRFPYYFDY (SEQ ID NO: 15).

15. The method of claim 12 , wherein the anti-hGM-CSF antibody lenzilumab comprises a VH CDR1 and a VH CDR2 as shown in a VH region having a sequence of VH #5 set forth in FIG. 1 .

16. The method of claim 12 , wherein the V-segment sequence has a VH V segment sequence of VH #5 shown in FIG. 1 .

17. The method of claim 12 , wherein the VH has the sequence of VH #5 set forth in FIG. 1 .

18. The method of claim 1 , wherein the anti-hGM-CSF antibody lenzilumab comprises a VL-region that comprises a CDR3 comprising the amino acid sequence FNK.

19. The method of claim 18 , wherein the anti-hGM-CSF antibody lenzilumab comprises a VL region that comprises a CDR3 comprising QQFNKSPLT (SEQ ID NO: 18).

20. The method of claim 11 , where the VL region comprises both a CDR1 and CDR2 of a VL region having the sequence of VK #2 shown in FIG. 1 .

21. The method of claim 18 , wherein the VL region comprises a V segment that has at least 95% identity to the VKIII A27 V-segment sequence as shown in FIG. 1 .

22. The method of claim 18 , wherein the VL region has the sequence of VK #2 set forth in FIG. 1 .

23. The method of claim 1 , wherein the anti-hGM-CSF antibody lenzilumab has a VH region CDR3 binding specificity determinant RQRFPY (SEQ ID NO: 12) and a VL region that has a CDR3 comprising QQFNKSPLT (SEQ ID NO: 18).

24. The method of claim 1 , wherein the anti-hGM-CSF antibody lenzilumab has a VH region having sequence VH #5 set forth in FIG. 1 and a VL region having sequence VK #2 set forth in FIG. 1 .

25. The method of claim 24 , wherein the VH region or the VL region, or both the VH and VL region amino acid sequences comprise a methionine at the N-terminus.

26. The method of claim 3 , wherein the CAR-T cells are CD19 CAR-T cells.

27. The method of claim 1 , wherein the reducing relapse rate or preventing occurrence of tumor relapse in the subject occurs in an absence of an incidence of immunotherapy-related toxicity.

28. The method of claim 1 , wherein the reducing relapse rate or preventing occurrence of tumor relapse in the subject occurs in a presence of an incidence of immunotherapy-related toxicity.

29. The method of claim 28 , wherein the immunotherapy-related toxicity is CAR-T related toxicity.

30. The method of claim 29 , wherein the CAR-T related toxicity is cytokine release syndrome, neurotoxicity or neuro-inflammation.

31. The method of claim 1 , wherein the tumor relapse occurrence is reduced by from 50% to 100% in the first one-quarter of a year after administering the recombinant GM-CSF antagonist compared to tumor relapse occurrence in a subject treated with immunotherapy and not administered a recombinant GM-CSF antagonist.

32. The method of claim 1 , wherein the tumor relapse occurrence is reduced by from 50% to 95% in the first half-year after administering the recombinant GM-CSF antagonist.

33. The method of claim 1 , wherein the tumor relapse occurrence is reduced by from 50% to 90% in the first year after administering the recombinant GM-CSF antagonist.

34. The method of claim 1 , wherein the tumor relapse occurrence is prevented long-term.

35. The method of claim 1 , wherein the tumor relapse occurrence is prevented by 12-36 months.

36. The method of claim 1 , wherein the tumor relapse occurrence is prevented completely (100%).

37. The method of claim 1 , wherein the subject has acute lymphoblastic leukemia.