Engineered cells for the production of cd4+ t cells and cd4+ tregs
AssigneeBlueRock Therapeutics LP
InventorsMathias Pawlak, Giulia Notarangelo, Chad Dufaud
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Abstract
This disclosure relates to engineered cells, artificial antigen presenting substrates (aAPSs), compositions and methods useful for producing CD4+ T cells and CD4+ Tregs from stem and/or progenitor cells. In particular, the disclosure relates to engineered cells, aAPSs, compositions and methods thereof, that can be used to facilitate CD4+ T cell formation. This disclosure also provides for the use of cells for treatment of patients with disease or in need of immune suppression.
Claims89
An engineered progenitor T cell comprising:
- a heterologous nucleic acid that, when activated, results in the expression of a lineage commitment factor at a level that is higher than that of a comparable wild-type cell to thereby facilitate differentiation towards a CD4+ T cell.
An engineered cell comprising:
- a heterologous nucleic acid comprising a coding sequence for a lineage commitment factor that promotes differentiation of the engineered cell towards a CD4+ T cell, wherein the heterologous nucleic acid is integrated within the genome of the engineered cell in a sustained transcriptionally active payload region (STAPLR) or a sustained transgene expression locus (STEL).
An engineered cell comprising a heterologous nucleic acid that, when activated, results in at least a 2-fold increase in expression of ThPOK as compared to a comparable wild-type cell under similar conditions, thereby promoting differentiation of the engineered cell towards a CD4+ T cell.
An artificial antigen presenting substrate (aAPS) comprising an immunomodulatory polypeptide.
A method of making a CD4+ T cell, the method comprising:
- activating a heterologous nucleic acid comprising a coding sequence for a lineage commitment factor within an engineered CD4−CD8− double negative (DN) cell or an engineered CD4+CD8+ double positive (DP) cell, wherein the activating results in an increased expression of said lineage commitment factor within the engineered DN cell or the engineered DP cell as compared to a comparable wild-type cell under similar conditions and thereby promotes the differentiation of the engineered DN cell or the engineered DP cell towards a CD4+ T cell.
A method of obtaining a population of cells enriched for CD4+ T cells, the method comprising:
- obtaining a CD4−CD8− (DN) cells or CD4+CD8+(DP) cells;
- and
- overexpressing at least one exogenous lineage commitment factor within the DN cells or DP cells as compared to a comparable wild-type cell under similar conditions to thereby produce a population of cells enriched for CD4+ T cells.
Dependencies are inferred from the claim text.