Method of modulating a chimeric antigen receptor t cell immune response by administering IL-10

• US 10,195,274 B2
• Filed: 03/20/2018
• Issued: 02/05/2019
• Est. Priority Date: 05/28/2015
• Status: Active Grant

• Current Assignee: Armo BioSciences Inc.
• Original Assignee: Armo BioSciences Inc.
• Inventors: Mumm, John Brian, Chan, Ivan Ho
• Primary Examiner(s): Stoica, Elly-Gerald
• Application Number:
  US15/926,118
• Publication Number:
  US 20180207270A1
• Time in Patent Office: 322 Days
• Field of Search: None
• CPC Class Codes: A61K 2039/5158 Antigen-pulsed cells, e.g. T-cells
• CPC Class Codes: A61K 2039/55527 Interleukins
• CPC Class Codes: A61K 38/2066 IL-10
• CPC Class Codes: A61K 39/39 characterised by the immunostimulating additives, e.g. chemical adjuvants
• CPC Class Codes: A61K 39/39558 against tumor tissues, cells, antigens
• CPC Class Codes: A61K 47/60 the organic macromolecular compound being a polyoxyalkylene oligomer, polymer or dendrimer, e.g. PEG, PPG, PEO or polyglycerol
• CPC Class Codes: A61K 9/0019 Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner non-active ingredients are additionally classified in A61K47/00
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: A61P 37/02 Immunomodulators
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: C07K 14/7051 T-cell receptor (TcR)-CD3 complex
• CPC Class Codes: C07K 16/30 from tumour cells
• CPC Class Codes: C07K 2317/73 Inducing cell death, e.g. apoptosis, necrosis or inhibition of cell proliferation
• CPC Class Codes: C07K 2319/02 containing a signal sequence
• CPC Class Codes: C07K 2319/03 containing a transmembrane segment
• CPC Class Codes: C12N 15/1136 against growth factors, growth regulators, cytokines, lymphokines or hormones
• CPC Class Codes: C12N 2310/14 interfering N.A.

Abstract

Methods of modulating immune responses in subjects having oncology- and immune-related diseases, disorders and conditions by the administration of an IL-10 agent, including pegylated IL-10.

Claims

1. A method of modulating a T cell-mediated immune response to a target cell population expressing a cell surface antigen in a subject, comprising:

a) administering to the subject a therapeutically effective amount of CD8+ T-cells genetically modified to express a chimeric antigen receptor (CAR T-cell), wherein the chimeric antigen receptor comprises;

at least one antigen-specific targeting region that specifically binds a cell surface antigen present on the target cell population,

a transmembrane domain, and

an intracellular signaling domain, and

b) administering to the subject a therapeutically effective amount of an IL-10 agent, wherein the IL-10 agent modulates T cell-mediated immune response to the target cell population.

2. The method of claim 1, wherein the intracellular signaling domain comprises a co-stimulatory domain.

3. The method of claim 1, wherein administration of the IL-10 agent to the subject is prior to administration of the therapeutically effective amount of CAR-T cells.

4. The method of claim 1, wherein administration of the IL-10 agent to the subject is simultaneously with administration of the therapeutically effective amount of CAR-T cells.

5. The method of claim 1, wherein administration of the IL-10 agent to the subject is subsequent to the administration of the therapeutically effective amount of CAR-T cells.

6. The method of claim 1, wherein the IL-10 agent is a PEG-IL-10.

7. The method of claim 6, wherein the PEG-IL-10 comprises at least one PEG molecule covalently attached to at least one amino acid residue of at least one monomer of IL-10.

8. The method of claim 6, wherein the PEG-IL-10 comprises a mixture of mono-pegylated and di-pegylated IL-10.

9. The method of claim 6, wherein the PEG component of the PEG-IL-10 has a molecular mass from 5 kDa to 30 kDa.

10. The method of claim 6, wherein the PEG component of the PEG-IL-10 has a molecular mass of at least 5 kDa.

11. The method of claim 6, wherein the PEG component of the PEG-IL-10 has a molecular mass of at least 20 kD.

12. The method of claim 1, wherein the IL-10 agent is administered subcutaneously.

13. The method of claim 1, wherein the amount of CD-8+ T-cells is obtained from the subject and genetically modified ex vivo.

14. The method of claim 1, wherein the target cell population comprises a tumor antigen.

15. The method of claim 14, wherein the tumor antigen is selected from the group consisting of CD19, CD20, CD22, ROR1, mesothelin, CD33/IL3Ra, c-Met, PSMA, Glycolipid F77, EGFRvIII, GD-2, NY-ESO-1 TCR, MAGE A3 TCR, or any combination thereof.

16. A method of treating a subject having a cancer-related disease, disorder or condition, comprising:

a) administering to the subject a therapeutically effective amount of CD8+ T-cells genetically modified to express a chimeric antigen receptor (CAR T-cell), wherein the chimeric antigen receptor comprises

at least one antigen-specific targeting region that specifically binds a cell surface tumor antigen present on a target tumor cell population,

a transmembrane domain,

an intracellular signaling domain, and

b) administering to the subject a therapeutically effective amount of an IL-10 agent.

17. The method of claim 16, wherein the intracellular signaling domain comprises a co-stimulatory domain.

18. The method of claim 16, wherein administration of the IL-10 agent is prior to administration of the therapeutically effective amount of CAR-T cells.

19. The method of claim 16, wherein administration of the IL-10 agent is simultaneously with administration of the therapeutically effective amount of CAR-T cells.

20. The method of claim 16, wherein administration of the IL-10 agent is subsequent to the administration of the therapeutically effective amount of CAR-T cells.

21. The method of claim 16, wherein the IL-10 agent is a PEG-IL-10.

22. The method of claim 21, wherein the PEG-IL-10 comprises at least one PEG molecule covalently attached to at least one amino acid residue of at least one monomer of IL-10.

23. The method of claim 21, wherein the PEG-IL-10 comprises a mixture of mono-pegylated and di-pegylated IL-10.

24. The method of claim 21, wherein the PEG component of the PEG-IL-10 has a molecular mass from 5 kDa to 30 kDa.

25. The method of claim 21, wherein the PEG component of the PEG-IL-10 has a molecular mass of at least 5 kDa.

26. The method of claim 21, wherein the PEG component of the PEG-IL-10 has a molecular mass of at least 20 kD.

27. The method of claim 16, wherein the IL-10 agent is administered subcutaneously.

28. The method of claim 16, wherein the CD-8+ T-cells are obtained from the subject and genetically modified ex vivo.