T cell progenitor having controlled expression of a transgene of interest
OwnerInna MENKOVAinventor
Life of this patent
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Abstract
The invention relates to a progenitor T cell comprising an expression cassette that enables controlled expression of a trans gene of interest based on the stage of maturation of said progenitor T cell. The invention also relates to a cell population enriched in progenitor T cells of this kind, to a process for preparing progenitor T cells, and to the use of said cells in a treatment method.
Claims21
1-16. (canceled)
An isolated T-cell progenitor having a CD45RA+, CD7+, CD5+ phenotype, the T-cell progenitor comprising an expression cassette which comprises an exogenous promoter induced by the Notch pathway functionally linked to a heterologous nucleic acid sequence of interest,
- wherein the exogenous promoter is chosen between the IL7RA and the BCL11B promoter.
An expression cassette comprising the IL7RA promoter functionally linked to a heterologous nucleic acid sequence of interest, wherein the nucleic acid sequence of interest encodes a chimeric antigen receptor or a T cell receptor.
An expression cassette comprising the BCL11B promoter functionally linked to a heterologous nucleic acid sequence of interest, wherein the nucleic acid sequence of interest encodes a chimeric antigen receptor or a T cell receptor.
The expression cassette according to claim 8, wherein the BCL11B promoter comprises or consists in a nucleic acid sequence having at least 85% identity with the nucleic acid sequence SEQ ID NO:
- 3.
A method of preparing the T-cell progenitor of claim 1, comprising the steps of:
- a) growingCD34+ hematopoietic stem cells in a culture medium comprising a Notch ligand such as Delta-like-1 (DLL1) or Delta-like-4 (DLL4) and cytokines for differentiating said CD34+ cells into T-cell progenitors having a CD45RA+, CD7+, CD5+ phenotype, preferably a CD45RA+, CD7+, CD5+, CD1a+ phenotype;
- b) transforming or transducing cells before, during or after said differentiation step (a) with a vector comprising an expression cassette,
- the expression cassette comprising an exogenous promoter induced by the Notch pathway functionally linked to a heterologous nucleic acid sequence of interest,
- the exogenous promoter being chosen between the IL7RA and the BCL11B promoter, and
- the nucleic acid sequence of interest encoding a chimeric antigen receptor or a T cell receptor;
- and
- wherein the CD34+ hematopoietic stem cells are derived from umbilical cord blood, peripheral blood or bone marrow.
A method of treatment of a cancer, an infectious disease, a genetic disease, an inflammatory disease or an immune or autoimmune disease comprising the administration of a T-cell progenitor to a subject in need thereof,
- the T-cell progenitor having a CD45RA+, CD7+, CD5+ phenotype and comprising an expression cassette which comprises an exogenous promoter induced by the Notch pathway functionally linked to a heterologous nucleic acid sequence of interest,
- wherein the exogenous promoter is chosen between the IL7RA and the BCL11B promoter.
Dependencies are inferred from the claim text.