US 2019/0161729 A1 · EX VIVO GENERATION OF GAMMA DELTA FOXP3+ REGULATORY T CELLS AND THERAPEUTIC USES THEREOF

Ex vivo generation of gamma delta foxp3+ regulatory t cells and therapeutic uses thereof

AssigneesInserm (Institut National De La Sante Et De La Recherche Medicale), Medecine Et Innovation, Universite Paris Diderot—Paris 7, Centre National de la Recherche Scientifique (CNRS)

InventorsDaniel ZAGURY, Helene LE BUANEC, Sophie DUCHEZ, Valerie SCHIAVON, Armand BENSUSSAN

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Abstract

The present invention relates to a method for ex vivo generating and expanding γδ Foxp3+ regulatory T cells, and therapeutic uses thereof. The inventors performed the induction of Foxp3− expression in ex vivo human induced tumor-antigen specific CD4+ TCRγδ unrestricted T cells and the induction of autologous CD8-mediated T-cell responses against tumor-antigen specific FOXP3 expressing CD4+ TCRγδ unrestricted T cells. The inventors developed a method to ex vivo generated and expanded antigen specific Foxp3 expressing CD3+ TCRγδ unrestricted T cells, committed to exclusively exert regulatory activity, whichever culture condition of stimulation is. In particular, the present invention relates to a method for generating ex vivo γδ Foxp3+ regulatory T cells having the following phenotype: CD3+ TCRγδ Foxp3+.

Claims18

Dependent claims

A method for generating ex vivo γδ Foxp3+ regulatory T cells having the following phenotype:

CD3+ TCRγδ+ Foxp3+, comprising
culturing CD3+ TCRγδ+ T cells in the presence of a γδ T cell activator and the following agents:
i) an cAMP (Cyclic adenosine monophosphate) activator, ii) a TGFβ (Transforming growth factor beta) pathway activator, and iii) a mTOR inhibitor, and optionally
iv) at least one cytokine selected from the group consisting of IL-2, IL-7, IL-15 and TSLP, and/or
v) at least one TET enzyme activator and/or
vi) at least one DNMT inhibitor,
for at least 5 days.

4 more elements

Dependencies are inferred from the claim text.

Facts

Application

16/320,764Filed 4 Aug 2017

Priority

EP 16196428.328 Oct 2016

Published

30 May 2019

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Classification21 codes

C12N 5/0637
T lymphocytes: immunosuppressive T lymphocytes, e.g. regulatory T cells or Treg
A61K 40/11
Characterised by the cell type used: t-cells, e.g. tumour infiltrating lymphocytes [TIL] or regulatory T [Treg] cells; Lymphokine-activated killer…
A61K 40/22
Characterised by the effect or the function of the cells: immunosuppressive or immunotolerising
A61K 40/42
Vertebrate antigens: cancer antigens