Method of increasing the efficacy of CAR-T immunotherapy using lenzilumab
Methods of inhibiting or reducing the incidence or the severity of immunotherapy-related toxicity in a subject, the method comprising a step of administering a recombinant hGMCSF antagonist to the subject, wherein said administering inhibits or reduces the incidence or the severity of immunotherapy-related toxicity in said subject, are provided. An hGMCSF antagonist for use in methods of inhibiting or reducing the incidence or the severity of immunotherapy-related toxicity in a subject also are provided.
1. A method of increasing the efficacy of CAR-T immunotherapy in a subject, the method comprising a step of administering a recombinant hGM-CSF antagonist to the subject, wherein the recombinant hGM-CSF antagonist is anti-hGM-CSF antibody lenzilumab, wherein said administering increases the efficacy of CAR-T immunotherapy in said subject.
2. The method of claim 1 , wherein said administering a recombinant hGM-CSF antagonist occurs prior to, concurrent with, or following said CAR-T immunotherapy or a combination thereof.
3. The method of claim 2 , wherein said increased efficacy comprises increased CAR-T cell expansion, reduced myeloid-derived suppressor cells (MDSC) that inhibit T-cell function, synergy with a checkpoint inhibitor, or any combination thereof.
4. The method of claim 3 , wherein said increased CAR-T cell expansion comprises at least a 50% increase compared to a control.
5. The method of claim 3 , wherein said increased CAR-T cell expansion comprises at least a one quarter log expansion compared to a control.
6. The method of claim 3 , wherein said increased cell expansion comprises at least a one half log expansion compared to a control.
7. The method of claim 3 , wherein said increased cell expansion comprises at least a one log expansion compared to a control.
8. The method of claim 3 , wherein said increased cell expansion comprises a greater than one log expansion compared to a control.
9. The method of claim 1 , wherein the anti-hGM-CSF antibody has a VH region CDR3 binding specificity determinant RQRFPY (SEQ ID NO: 12) or RDRFPY and a VL region having a CDR3 comprising QQFNKSPLT (SEQ ID NO: 18).
10. The method of claim 9 , wherein the anti-hGM-CSF antibody 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 .
11. The method of claim 9 , wherein the CDR3 comprises RQRFPYYFDY (SEQ ID NO: 15).
12. The method of claim 9 , wherein the anti-hGM-CSF antibody 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 .
13. The method of claim 9 , where the VL region comprises a CDR1 and CDR2 of a VL region having the sequence of VK #2 shown in FIG. 1 .
14. The method of claim 1 , where the anti-hGM-CSF antibody 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 .
15. The method of claim 14 , where the VH region or the VL region, or both the VH and VL region amino acid sequences comprise a methionine at the N-terminus.
16. The method of claim 1 , wherein the CAR-T immunotherapy comprises CD19 CAR-T cells.