T cells

Abstract

The present invention relates to T cells and tissue-resident memory T cells (T RM The present invention relates to a method for producing tissue-resident memory T cells (T RM ) itself, these T RM The use of these T cells in compositions containing the cells, as well as in therapies such as immunotherapy for the treatment of cancer. RM Uses of the cells and compositions.

Claims

1. A tissue-resident memory T cell (T) cell culture method comprising the step of culturing T lymphocytes in the presence of transforming growth factor beta (TGFβ) and interleukin-7 (IL-7). ＲＭ A method for producing ) wherein T lymphocytes are obtained from blood, the method described above.

2. The method according to claim 1, wherein T lymphocytes are co-cultured with regulatory T cells.

3. T lymphocytes are cultured in the presence of TGFβ, and / or T lymphocytes are not co-cultured with regulatory T cells, and / or T lymphocytes are naive, effector, or memory CD8+ T lymphocytes, and / or TGFβ is present at concentrations between 0.01 ng / ml and 50 ng / ml, and / or T lymphocytes are obtained from the blood of humans or non-human animals. The method according to claim 1 or 2.

4. T ＲＭ The method according to any one of claims 1 to 3, characterized by: the expression of differentiation cluster 8 (CD8), differentiation cluster 69 (CD69), Hobit, aryl hydrocarbon receptor (AhR), and / or differentiation cluster 103 (CD103); and / or the absence of expression of killer cell lectin-like receptor subfamily G member (KLRG1) and / or eomesodermine (Eomes).

5. The method according to any one of claims 1 to 4, comprising the step of culturing T lymphocytes in the presence of IL-2, IL-4, IL-12, IL-15, IL-21, and / or IL-33.

6. The method according to any one of claims 1 to 4, further comprising the step of culturing T lymphocytes in the presence of at least one interleukin 1 family member.

7. The method according to claim 6, wherein at least one interleukin-1 family member is IL-1a, IL-1b, and / or IL-18.

8. The method according to any one of claims 1 to 7, wherein T lymphocytes are cultured in a medium containing at least one aryl hydrocarbon receptor (AhR) ligand.

9. The method according to claim 8, wherein the AhR ligand is selected from halogenated aromatic hydrocarbons, polycyclic aromatic hydrocarbons, dietary aryl hydrocarbons, heme metabolites, indigoids, StemRegenin 1, and tryptophan metabolites.

10. The method according to any one of claims 1 to 9, wherein T lymphocytes are cultured in a medium containing at least one lipid and / or an antigen.

11. The method according to claim 10, wherein the antigen is a tumor antigen.

12. The method according to any one of claims 1 to 11, wherein regulatory T cells are characterized by or absent by the expression of Foxp3.

13. The method according to any one of claims 1 to 12, further comprising the step of culturing T lymphocytes together with dendritic cells.

14. Tissue-resident memory T cells (T ＲＭ The method according to any one of claims 1 to 13, further comprising the step of propagating a population of ).

15. In the presence of IL-2, IL-4, IL-12, IL-15 and / or IL-21, T ＲＭ The method according to claim 10, further comprising the step of culturing cells.

16. Tissue-resident memory T cells (T) obtained by the method described in any one of claims 1 to 15 ＲＭ ).

17. Tissue-resident memory T cells (T) according to claim 16 for use in treatment ＲＭ ) or its population.

18. T ＲＭ Tissue-resident memory T cells (T) for use in T cell therapy according to claim 17. ＲＭ ).

19. Tissue-resident memory T cells according to claim 16, for use in the prevention, treatment, or improvement of cancer or infectious diseases.

20. A pharmaceutical composition comprising tissue-resident memory T cells or a proliferating population thereof as described in claim 16, and a pharmaceutically acceptable excipient.

21. A method for producing the pharmaceutical composition according to claim 20, comprising the step of combining a therapeutically effective amount of tissue-resident memory T cells or a proliferating population thereof according to claim 16 with a pharmaceutically acceptable excipient.

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