Immunomodulatory cells and compositions
CD62L- granulocyte-producing cells with specific biomarker profiles are used to amplify therapeutic immune responses, addressing the lack of effective modulation in existing technologies and offering improved treatment for cancer and infections.
Patent Information
- Application Number
- HK62026124587
- Authority / Receiving Office
- HK · HK
- Patent Type
- Applications
- Current Assignee / Owner
- Priority Date
- 2023-07-24
- Filing Date
- 2026-06-09
- Publication Date
- 2026-07-31
AI Technical Summary
Existing technologies lack effective methods to modulate therapeutic immune responses, particularly non-granulocyte-mediated responses, for treating cancer and infections.
Utilization of CD62L- granulocyte-producing cells or populations with specific biomarker expression profiles (CD10-, CD11b-, CD16-, CD62L-, CD66b-, CD177-, CD15+, CD38+, CD49d+, CD54+, CD63+) to amplify therapeutic immune responses.
Enhances therapeutic immune responses, providing effective treatment options for cancer and infections through the use of CD62L- granulocyte-producing cells with defined biomarker profiles.
Smart Images
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Abstract
Description
This abstract provides information on granulocyte-producing cells or populations of such cells for modulating therapeutic immune responses. Therapeutic immune responses can be non-granulocyte-mediated. Granulocyte-producing cells or populations of such cells can be used to amplify therapeutic immune responses, such as non-granulocyte-mediated responses. Granulocyte-producing cells or cell populations can be CD62L-. Granulocyte-producing cells or cell populations can have a biomarker expression profile: CD10-, CD11b-, CD16-, CD62L-, CD66b-, CD177-, CD15+, CD38+, CD49d+, CD54+, CD63+. Granulocyte-producing cells or cell populations can be used to treat cancer or infections.
Claims
CLAIMS1. A granulopoietic cell, or a population of such cells, for use to modulate a therapeutic immune response.
2. A granulopoietic cell, or population of such cells, for use according to claim 1 , wherein the cell is CD62L'.
3. A granulopoietic cell, or a population of such cells, for use according to claim 1 or claim 2, wherein the granulopoietic cell or population of such cells has a marker expression profile: CD10-, CD11b-, CD16-, CD62L’, CD66b’, CD177’, CD15+, CD38+, CD49d+, CD54+, CD63+;4. A granulopoietic cell, or a population of such cells, for use according to claim 1 or claim 2, wherein the granulopoietic cell has a marker expression profile CD11 bhiCD15+CD66b+CD177+CD18hiCD16- CD34’ CD38’ CD49d-;5. A granulopoietic cell, or a population of such cells, for use according to claim 1 or claim 2, wherein the granulopoietic cell has a marker expression profile CD34+ / _, CD38+ / _, CD15+ / _, CD49d+, CD18+, CD66b’, CD177’, CD16’.
6. A granulopoietic cell, or a population of such cells, for use according to claim 1 or claim 2, wherein the granulopoietic cell or population of such cells has a marker expression profile: CD10-, CD11b-, CD16-, CD62L', CD66b’, CD177’, CD15+, CD38+, CD49d+, CD54+, CD63+.
7. A granulopoietic cell, or a population of such cells, for use according to claim 1 or claim 2, wherein the granulopoietic cell or population of such cells has a marker expression profile: CD11bhiCD15+CD66b+CD177+CD18hiCD16’ CD34’ CD38’ CD49d\8. A granulopoietic cell, or a population of such cells, for use according to claim 1 or claim 2, wherein the granulopoietic cell or population of such cells has a marker expression profile: CD34+ / -, CD38+ / -, CD15+ / -, CD49d+, CD18+, CD66b’, CD177 CD16’.
9. A granulopoietic cell, or a population of such cells, for use according to any preceding claim, to amplify a therapeutic immune response.
10. A granulopoietic cell, or a population of such cells, for use according to any preceding claim, to modulate a non-granulocytic immune response.
11. A granulopoietic cell, or a population of such cells, for use according to any preceding claim, wherein the granulopoietic cell is capable of differentiating into granulocytes with the ability to kill cancer cells.
12. A granulopoietic cell, or a population of such cells, for use according to any preceding claim, wherein the therapeutic immune response is a host therapeutic immune response.
13. A granulopoietic cell, or a population of such cells, for use according to any preceding claim, wherein the granulopoietic cell is allogeneic14. A granulopoietic cell, or a population of such cells, for use according to any preceding claim, wherein the granulopoietic is able to differentiate to produce a cell that secretes CXCL10 and / or expresses a ligand for a costimulatory molecule selected from the group consisting of: 4-1 BBL; and OX40L.
15. A granulopoietic cell, or a population of such cells, for use according to any preceding claim, for use in the treatment of cancer.
16. A granulopoietic cell, or a population of such cells, for use according to claim 10, wherein the cancer is selected from the group consisting of: pancreatic cancer, liver cancer, oesophageal cancer, stomach cancer, cervical cancer, ovarian cancer, lung cancer, bladder cancer, kidney cancer, brain cancer, prostate cancer, myeloma cancer, non-Hodgkin’s lymphoma (NHL), larynx cancer, uterine cancer, and breast cancer.
17. A granulopoietic cell, or a population of such cells, for use according to any preceding claim, for use in the treatment of an infection.
18. A granulopoietic cell, or a population of such cells, for use according to claim 12, wherein the infection is selected from the group consisting of: a viral infection; a bacterial infection; and a fungal infection.
19. A granulopoietic cell, or a population of such cells, for use according to any preceding claim, for use to amplify a non-granulocytic therapeutic immune response by increasing activation of non-granulocyte immune cells.
20. A granulopoietic cell, or a population of such cells, for use according to claim 14, wherein the activation increases expression by the immune cells of a degranulation marker selected from the group consisting of: CD107a; perforin; and granzymes.
21. A granulopoietic cell, or a population of such cells, for use according to claim 14 or claim 15, wherein the activation increases expression by the immune cells of a costimulatory molecule selected from the group consisting of: 4-1 BB; 0X40; CD27; CD28; ICOS; HVEM; LIGHT; CD40L; DR3; GITR; CD30; TIM1 ; CD2; and CD226.
22. A granulopoietic cell, or a population of such cells, for use according to any preceding claim, for use to amplify a therapeutic immune response by increasing activation of T cells.
23. A granulopoietic cell, or a population of such cells, for use according to claim 17, wherein the T cells are selected from the group consisting of: a CD8+T cell; a CD4+T cell; a NK T cell; an op T cell; a yb T cell; a peripheral blood T cell; and a tumour infiltrated T cell.
24. A granulopoietic cell, or a population of such cells, for use according to any preceding claim, for use to amplify a therapeutic immune response by increasing activation of NK cells.
25. A granulopoietic cell, or a population of such cells, for use according to any preceding claim, for use to amplify a therapeutic immune response by increasing activation of PBMCs.
26. A granulopoietic cell, or a population of such cells, for use according to any preceding claim, for use to amplify a therapeutic immune response by increasing activation of TILs.
27. A granulopoietic cell, or a population of such cells, for use according to any preceding claim, for use to amplify a therapeutic immune response by increasing tumour cell killing activity of immune cells.
28. A granulopoietic cell, or a population of such cells, for use according to any preceding claim, for use to amplify a therapeutic immune response by increasing proliferation of immune cells.
29. A granulopoietic cell, or a population of such cells, for use according to any preceding claim, for use in combination with a further cell immunotherapy.
30. A method of promoting therapeutic activity of non-granulocytic immune cells, the method comprising incubating a non-granulocytic immune cell with a granulopoietic cell, or a population of such cells, as defined in any preceding claim.
31. A pharmaceutical composition comprising an enriched population of granulopoietic cells as defined in any of claims 1 to 29.
32. A method of selecting a suitable treatment regimen for a patient, the method comprising:• identifying whether the patient has an impaired non-granulocytic immune response; wherein• if the patient is identified as having an impaired non-granulocytic immune response, then treatment with a granulopoietic cell is selected as an appropriate treatment; and• if the patient is identified as lacking an impaired non-granulocytic immune response, then treatment with a therapy other than a granulopoietic cell is selected.
33. A method of selecting a suitable treatment regimen for a patient, the method comprising:• incubating a non-granulocytic immune cell from the patient with a granulopoietic cell; wherein• if the activity of the non-granulocytic immune cell from the patient is increased in response to the incubation, then treatment with a granulopoietic cell is selected as an appropriate treatment; and if the activity of the non-granulocytic immune cell from the patient is increased in response to the incubation, then treatment with a therapy other than a granulopoietic cell is selected.
34. A method of increasing survival of immune cells in culture, the method comprising, culturing the immune cells in the presence of a feeder layer of granulopoietic cells. method of increasing proliferation of immune cells in culture, the method comprising, culturing the immune cells in the presence of a feeder layer of granulopoietic cells.
35. A method of identifying whether or not a granulopoietic cell is suitable for use in the treatment of cancer by beneficially modulating the tumour microenvironment, the method comprising:• assessing whether the granulopoietic cell, or a cell derived from the granulopoietic cell, is able to express proinflam matory cytokines; and / or• assessing whether the granulopoietic cell, or a cell derived from the granulopoietic cell, is able to stimulate expression of proinflammatory cytokines by non-granulocytic immune cells; and identifying whether or not a granulopoietic cell is suitable for use in the treatment of cancer by beneficially modulating the tumour microenvironment on the basis of this assessment.
36. A method of identifying whether or not a granulopoietic cell is suitable for use in the treatment of cancer by increasing recruitment of immune cells into a tumour and / or immune cell activation, the method comprising:• assessing whether the granulopoietic cell, or a cell derived from the granulopoietic cell, is able to express a chemokine associated with promoting cell trafficking; and / or• assessing whether the granulopoietic cell, or a cell derived from the granulopoietic cell, is able to stimulate expression of degranulation markers by non-granulocytic immune cells; and identifying whether or not a granulopoietic cell is suitable for use in the treatment of cancer by increasing recruitment of immune cells into a tumour and / or immune cell activation on the basis of this assessment37. A method of identifying whether or not a granulopoietic cell is suitable for use in the treatment of cancer by directly promoting killing of cancer cells, the method comprising:• incubating the granulopoietic cell, or a cell derived from the granulopoietic cell, with cells of a cancer cell line; and• assessing whether the granulopoietic cell, or a cell derived from the granulopoietic cell, is able to increase death of the cells of the cancer cell line to a greater extent than death of non-cancer cells; and identifying whether or not a granulopoietic cell is suitable for use in the treatment of cancer by directly promoting killing of cancer cells on the basis of this assessment.
38. A method of identifying whether or not a granulopoietic cell is suitable for use in the treatment of infection by directly promoting killing of cellular infectious agents or infected cells, the method comprising:• incubating the granulopoietic cell, or a cell derived from the granulopoietic cell, with a sample of a cellular infectious agent or of infected cells; and• assessing whether the granulopoietic cell, or a cell derived from the granulopoietic cell, is able to increase death of the cellular infectious agent or of infected cells ;and identifying whether or not a granulopoietic cell is suitable for use in the treatment of infection by directly promoting killing of cellular infectious agents or infected cells on the basis of this assessment.
39. A method of identifying whether or not a granulopoietic cell is suitable for use in treatment by amplifying a therapeutic immune response, the method comprising:• incubating the granulopoietic cell, or a cell derived from the granulopoietic cell, with immune cells; and• assessing whether the granulopoietic cell is able to increase activation of the immune cells; and identifying whether or not a granulopoietic cell is suitable for use in the treatment by amplifying a therapeutic immune response on the basis of this assessment.
40. A method of preparing granulopoietic cells for therapeutic use, the method comprising:• culturing a population of progenitor cells in cell culture conditions that promote differentiation of the progenitor cells comprising the presence of:• G-CSF,• GM-CSF,• IL-3 and• TNF; to produce a population of granulopoietic cells.
41. A population of granulopoietic cells prepared for therapeutic use by a method according to claim 40.
42. An immortalised cell line obtainable (e.g. obtained) from a selected stem cell, or a stable stem cell culture