Methods of Treating CD127-Positive Cancer by Administering Anti-CD127 Agents

Abstract

The present invention relates to the field of immunotherapy. The present invention provides a novel clinical use of anti-CD127 agents, particularly anti-CD127 antibodies or related compounds, for the treatment and / or prevention of cancer. The present invention relates to a method for treating patients with CD127-positive cancer, particularly CD127-positive leukemia or CD127-positive solid tumors, by administering to the patient a therapeutic dose of an anti-CD127 agent, which has the ability to enhance the antibody-dependent cellular phagocytosis (ADCP) activity of macrophages targeting CD127-positive cancer cells, and does not have antibody-dependent cellular cytotoxicity (ADCC) activity, particularly against immune cells, especially against T cells.

Claims

**Claim 1**: A pharmaceutical composition for enhancing and / or inducing phagocytosis of CD127-positive tumor cells in a patient, comprising a therapeutically effective amount of an anti-CD127 agent, wherein the anti-CD127 agent has antibody-dependent cell phagocytosis (ADCP) activity against CD127-positive tumor cells and does not have antibody-dependent cell cytotoxicity (ADCC) activity. **Claim 2**: The pharmaceutical composition according to claim 1, wherein the anti-CD127 agent is an anti-CD127 antibody or an antigen-binding fragment thereof or an antigen-binding antibody mimetic. **Claim 3**: The pharmaceutical composition according to claim 1, wherein phagocytosis of CD127-positive tumor cells in the patient by macrophages is enhanced and / or induced. **Claim 4**: The pharmaceutical composition according to claim 1, wherein the anti-CD127 agent has antibody-dependent cell phagocytosis (ADCP) activity by macrophages against CD127-positive tumor cells. **Claim 5**: The pharmaceutical composition according to claim 1, wherein the anti-CD127 agent does not have antibody-dependent cell cytotoxicity (ADCC) activity against immune cells, especially against T cells. **Claim 6**: The pharmaceutical composition according to claim 1, wherein the CD127-positive cancer is leukemia, especially acute lymphoblastic leukemia (ALL), especially T-cell ALL or B-cell ALL. **Claim 7**: The pharmaceutical composition according to claim 1, wherein the CD127-positive cancer is selected from the group consisting of CD127-overexpressing acute lymphoblastic leukemia (ALL), CD127 and / or JAK-STAT pathway mutant ALL, BCR-ABL1-like ALL, and B-cell precursor ALL having one of the cytogenetics of t(1;19), t(12,21), MLL rearrangement, hyperdiploid karyotype, trisomy 4, and trisomy 10. **Claim 8**: The pharmaceutical composition according to claim 1, wherein the CD127-positive cancer is derived from a solid cancer, especially mesothelioma. **Claim 9**: The pharmaceutical composition according to claim 1, wherein the anti-CD127 agent does not induce lymphopenia in the patient. **Claim 10**: The pharmaceutical composition according to claim 1, wherein the anti-CD127 agent is an anti-CD127 antibody or an antigen-binding fragment thereof comprising a constant chain belonging to the subclass of IgG1, IgG2, IgG3, or IgG4, especially the subclass of mammalian IgG1, IgG2, IgG3, or IgG4, especially the subclass of mammalian IgG4.

11. The pharmaceutical composition according to claim 1, wherein the anti-CD127 agent is selected from the group consisting of a chimeric antibody, a humanized antibody, and a fully human monoclonal antibody.

12. The anti-CD127 agent is at least - VH CDR1 SEQ ID NO: 3, - VH CDR2 SEQ ID NO: 4, - VH CDR3 SEQ ID NO: 5 or SEQ ID NO: 6 of the VH chain containing the amino acid sequence and at least - VL CDR1 SEQ ID NO: 7 or SEQ ID NO: 8, - VL CDR2 SEQ ID NO: 9 or SEQ ID NO: 10, - VL CDR3 SEQ ID NO: 11 of the VL chain containing the amino acid sequence The pharmaceutical composition according to claim 1, which is an anti-CD127 antibody or an antigen-binding fragment thereof.

13. The pharmaceutical composition according to claim 1, wherein the anti-CD127 antibody or an antigen-binding fragment thereof is an antagonist of the IL-7R signaling pathway induced by the binding of IL-7 to CD127.

14. The pharmaceutical composition according to claim 1, wherein the anti-CD127 agent is used in combination with a conventional treatment for cancer.

15. The pharmaceutical composition according to claim 1, in particular in combination with at least one second therapeutic agent selected from the group consisting of chemotherapeutic agents, targeted cancer therapy agents, immunotherapeutic agents, and radiation therapy agents, for simultaneous, separate, or sequential use.

16. The pharmaceutical composition according to claim 15, wherein the at least one second therapeutic agent is selected from the group consisting of cytotoxic agents, chemotherapeutic agents, anti-angiogenic agents, cell cycle control / apoptosis regulators, hormone regulators, and anti-cancer immunogens, in particular anti-cancer antibodies, especially tumor-targeted antibodies.

17. For use particularly simultaneously, separately or sequentially, an anti-CD3 agent, particularly an anti-CD3 antibody, an anti-PD1 agent, particularly an anti-PD1 antibody, an anti-PDL1 agent, particularly an anti-PDL1 antibody, an anti-CTLA4 agent, particularly an anti-CTLA4 antibody, an agonist of CD137, particularly an agonist anti-CD137 antibody, an anti-VEGF agent, particularly an anti-VEGF antibody, an anti-CLEC-1 agent, particularly an anti-CLEC-1 antibody, an anti-CD28 agent, particularly an anti-CD28 antibody, an anti-CD19 agent, particularly an anti-CD19 antibody, and an anti-CD47 agent, particularly an anti-CD47 antibody, an anti-SIRPa agent, particularly an anti-SIRPa antibody, an anti-Bcl-2 agent, particularly venetoclax, an inhibitor of the tyrosine / kinase pathway, dexamethasone, rituximab, trastuzumab, cetuximab, nelarabine, asparaginase Erwinia chrysanthemi (or erwinase), asparas (or caraspase pegol-mknl), besponsa (inotuzumab ozogamicin), blinatumomab (or blincyto), and cerubidine (or daunorubicin hydrochloride or rubidomycin), clofarabine (or chloral), cyclophosphamide, cytarabine, dasatinib (or sprycel), doxorubicin hydrochloride, gleevac (imatinib mesylate), iclusig (ponatinib hydrochloride), inotuzumab ozogamicin, imatinib mesylate, kimria (or tisagenlecleucel), vincristine, marqibo (vincristine sulfate liposome), mercaptopurine (or purinethol or purxan), methotrexate sodium (or trexall), nelarabine, oncaspar (or pegaspargase or PEG-asparaginase), ponatinib hydrochloride, prednisone, purinethol (mercaptopurine), vincristine sulfate, vincristine sulfate liposome, the pharmaceutical composition according to claim 1, in combination with at least one second therapeutic agent selected from the group consisting of.

18. The pharmaceutical composition according to claim 17, wherein at least one second therapeutic agent is dexamethasone and / or oncaspar (or pegaspargase or PEG-asparaginase) and / or vincristine, particularly dexamethasone and oncaspar (or pegaspargase or PEG-asparaginase) and vincristine.

19. The pharmaceutical composition according to claim 1, wherein after the patient is evaluated as having CD127-positive tumor cells, an anti-CD127 agent is administered to the patient.

20. A pharmaceutical composition for treating a patient having CD127-positive cancer comprising CD127-positive tumor cells and comprising an anti-CD127 agent, wherein the anti-CD127 agent has antibody-dependent cell phagocytosis (ADCP) activity against CD127-positive tumor cells and does not have antibody-dependent cell cytotoxicity (ADCC) activity.

21. The pharmaceutical composition according to claim 20, wherein the CD127-positive cancer is treated by phagocytosis of CD127-positive tumor cells.

22. The pharmaceutical composition according to claim 20, wherein the anti-CD127 agent is an anti-CD127 antibody or an antigen-binding fragment thereof or an antigen-binding antibody mimetic.

23. The pharmaceutical composition according to claim 20, wherein phagocytosis of the patient's CD127-positive tumor cells by macrophages is enhanced and / or induced.

24. The pharmaceutical composition according to claim 20, wherein the anti-CD127 agent has antibody-dependent cell phagocytosis (ADCP) activity against CD127-positive tumor cells by macrophages.

25. The pharmaceutical composition according to claim 20, wherein the anti-CD127 agent does not have antibody-dependent cell cytotoxicity (ADCC) activity against immune cells, especially against T cells.

26. The pharmaceutical composition according to claim 20, wherein the patient has a CD127-positive cancer selected from the group consisting of leukemia, especially acute lymphoblastic leukemia (ALL), especially T-cell ALL or B-cell ALL, and solid cancer, especially mesothelioma.

27. The pharmaceutical composition according to claim 20, in combination with a conventional treatment of cancer.

28. The pharmaceutical composition according to claim 20, in combination with at least one second therapeutic agent selected from the group consisting of chemotherapeutic agents, targeted cancer therapy agents, immunotherapeutic agents and radiation therapy agents, especially for simultaneous, separate or sequential use.

29. The pharmaceutical composition according to claim 20, wherein the anti-CD127 agent is defined according to any one of claims 9 to 13.

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