Genetically Engineered Cells and Uses Thereof
AssigneeCentury Therapeutics, Inc.
InventorsMichael Naso, Jill Carton, Mark Wallet, Barry Morse, Luis Borges, Hillary Quinn, Liam Campion, Buddha Gurung, Heidi Jessup, Kenneth Brasel, Lucas Thompson
Life of this patent
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Abstract
Provided are genetically engineered induced pluripotent stem cells (iPSCs) and derivative cells thereof expressing a chimeric antigen receptor (CAR) and methods of using the same. Also provided are compositions, polypeptides, vectors, and methods of manufacturing.
Claims46
An induced pluripotent stem cell (iPSC) or a derivative cell thereof comprising:
- (i) a first exogenous polynucleotide encoding a chimeric antigen receptor (CAR) targeting a CD19 antigen;
- (ii) a second exogenous polynucleotide encoding an inactivated cell surface receptor that comprises a monoclonal antibody-specific epitope and an interleukin 15 (IL-15), wherein the inactivated cell surface receptor and the IL-15 are operably linked by an autoprotease peptide;
- and
- (iii) a deletion or reduced expression of one or more of B2M, TAP 1, TAP 2, Tapasin, RFXANK, CIITA, RFX5 and RFXAP genes.
(canceled)
An induced pluripotent stem cell (iPSC), a natural killer (NK) cell or a T cell comprising:
- (i) a first exogenous polynucleotide encoding a chimeric antigen receptor (CAR) having the amino acid sequence of SEQ ID NO:
- 61;
- (ii) a second exogenous polynucleotide encoding a truncated epithelial growth factor (tEGFR) variant having the amino acid sequence of SEQ ID NO:
- 71, an autoprotease peptide having the amino acid sequence of SEQ ID NO:
- 73, and interleukin 15 (IL-15) having the amino acid sequence of SEQ ID NO:
- 72;
- and
- (iii) optionally, a third exogenous polynucleotide encoding a human leukocyte antigen E (HLA-E) having the amino acid sequence of SEQ ID NO:
- 66;
- wherein the first, second and third exogenous polynucleotides are integrated at loci of AAVS1, CIITA and B2M genes, to thereby delete or reduce expression of CIITA and B2M.
A method of differentiating an induced pluripotent stem cell (iPSC) into an NK cell, comprising subjecting the iPSC to a differentiation protocol including culturing the cell in a medium containing a recombinant human IL-12 for the final 24 hours of culturing under the differentiation protocol.
A CD34+ hematopoietic progenitor cell (HPC) derived from an induced pluripotent stem cell (iPSC) comprising:
- (i) a first exogenous polynucleotide encoding a chimeric antigen receptor (CAR) targeting a CD19 antigen;
- (ii) a second exogenous polynucleotide encoding an inactivated cell surface receptor that comprises a monoclonal antibody-specific epitope and an interleukin 15 (IL-15), wherein the inactivated cell surface receptor and the IL-15 are operably linked by an autoprotease peptide;
- and
- (iii) a deletion or reduced expression of one or more of B2M, TAP 1, TAP 2, Tapasin, RFXANK, CIITA, RFX5 and RFXAP genes.
The CD34+ HPC according to claim 0, further comprising a third exogenous polynucleotide encoding a human leukocyte antigen E (HLA-E) and/or human leukocyte antigen G (HLA-G).
The CD34+ HPC according to claim 0, wherein one or more of the exogenous polynucleotides are integrated at the loci of the CIITA, AAVS1 and B2M genes.
Dependencies are inferred from the claim text.