C12N2501/06

METHODS FOR REPROGRAMMING CELLS AND USES THEREOF
20230227785 · 2023-07-20 ·

A method of obtaining a pluripotent-like multipotent cell, including providing a cell of a first type which is not a pluripotent-like multipotent cell; contacting the cell of a first type with an agent capable of remodeling the chromatin and/or DNA of the cell; transiently increasing expression of at least one pluripotent gene regulator in the cell of a first type, to a level at which the at least one pluripotent gene regulator is capable of driving transformation of the cell of a first type into the pluripotent-like multipotent cell; and placing or maintaining the cell in a differentiation medium and maintaining intracellular levels of the at least one pluripotent gene regulator for a sufficient period of time to allow a stable pluripotent-like multipotent cell to be obtained; wherein the pluripotent-like multipotent cell so obtained does not exhibit teratoma formation in vivo.

Engineered T Cells

A therapeutic molecule (single chain-based antibody or ligand-based) optimized for expression and secretion from engineered T cells, which may be gamma delta (gd) T cells. When expressed from engineered gdT cells, the STAR will be secreted and mediate engagement between gdT cells and antigen/receptor on target cells. Binding mediates the formation of a cytolytic synapse between the gdT cell and the target cell leading to activation the gdT cells to release proteolytic enzymes that kill target cells.

Histone deacetylase (HDAC) inhibitor up-regulates car expression and targeted antigen intensity, increasing antitumor efficacy

Embodiments of the invention employ methods and compositions for enhancing potency of immune cells that express one or more therapeutic proteins. In certain cases, the methods modulate expression of a CAR transgene in an immune cell, such as a T cell. Specific embodiments employ the exposure of cells and/or individuals to be treated with the cells with an effective amount of at least one agent that upregulates expression of the therapeutic protein, such as a mitogen, histone deacetylase inhibitor, and or DNA methyltransferase inhibitor.

Combination therapy for a stable and long term engraftment

A method of treating a subject in need of a non-syngeneic cell or tissue graft is disclosed. The method comprising: (a) transplanting into a subject a dose of T cell depleted immature hematopoietic cells, wherein the T cell depleted immature hematopoietic cells comprise less than 5×10.sup.5 CD3.sup.+ T cells per kilogram body weight of the subject, and wherein the dose comprises at least about 5×10.sup.6 CD34+ cells per kilogram body weight of the subject; and subsequently (b) administering to the subject a therapeutically effective amount of cyclophosphamide, wherein the therapeutically effective amount comprises 25-200 mg per kilogram body weight, thereby treating the subject.

COMBINATION THERAPY FOR A STABLE AND LONG TERM ENGRAFTMENT

A method of treating a subject in need of a non-syngeneic cell or tissue graft is disclosed. The method comprising: (a) transplanting into a subject a dose of T cell depleted immature hematopoietic cells, wherein the T cell depleted immature hematopoietic cells comprise less than 5×10.sup.5 CD3.sup.+ T cells per kilogram body weight of the subject, and wherein the dose comprises at least about 5×10.sup.6 CD34+ cells per kilogram body weight of the subject; and subsequently (b) administering to the subject a therapeutically effective amount of cyclophosphamide, wherein the therapeutically effective amount comprises 25-200 mg per kilogram body weight, thereby treating the subject.

Lineage Reprogramming to Induced Cardiac Progenitor Cells (iCPC) By Defined Factors
20230038168 · 2023-02-09 ·

Animal cells, notably adult fibroblasts, are advantageously reprogrammed in direct lineage reprogramming methods using defined factors to produce proliferative and multipotent induced cardiac progenitor cells (iCPC). The iCPC thus produced can be differentiated under suitable differentiation conditions to cardiac lineage cells including cardiomyocytes, smooth muscle cells, and endothelial cells, as evidenced by expression of lineage specific markers. Sets of factors effective in combination to reprogram the fibroblasts can include a set that includes some or all of 5 factors (Mesp1, Baf60c, Nkx2.5, Gata4, Tbx5), a set that includes some or all of 11 factors (Mesp1, Mesp2, Gata4, Gata6, Baf60c, SRF, Isl1, Nkx2.5, Irx4, Tbx5, Tbx20), a set that includes some or all of 18 factors (T, Mesp1, Mesp2, Tbx5, Tbx20, Isl1, Gata4, Gata6, Irx4, Nkx2.5, Hand1, Hand2, Tbx20, Tbx18, Tip60, Baf60c, SRF, Hey2), and a set that includes some or all of 22 factors (T, Mesp1, Mesp2, Tbx5, Tbx20, Isl1, Gata4, Gata6, Irx4, Nkx2.5, Hand1, Hand2, Tbx20, Tbx18, Tip60, Baf60c, SRF, Hey2, Oct4, Klf4, Sox2, L-myc).

XENO-FREE AND TRANSGENE-FREE REPROGRAMING OF MESENCHYMAL STEM CELLS TOWARD NEURAL PROGENITOR CELLS
20220348867 · 2022-11-03 ·

Disclosed herein are methods and materials for transdifferentiating mesenchymal stem cells into neural progenitor cells.

SCAFFOLDS TO TREAT SOLID TUMOR CELLS AND ESCAPE VARIANTS
20220339195 · 2022-10-27 ·

Implantable scaffolds that treat solid tumors and escape variants and that provide effective vaccinations against cancer recurrence are described. The scaffolds include genetically-reprogrammed lymphocytes and a lymphocyte-activating moiety.

Vacuole-inducing compounds, methods of making and using the same

Vacuole- or exosome-inducing indole-based chalcone and substituted triazole-hydrazone compounds that induce endosomal vacuolization and increase exosome yield, but do not trigger growth arrest or cell death, and methods of making and using are described.

POPULATIONS OF ENRICHED REGULATORY T CELLS AND METHODS FOR PRODUCING SAME
20230066340 · 2023-03-02 ·

Provided herein are populations of enriched ex vivo expanded umbilical cord blood-derived regulatory T cells. Also provided are methods of making and using the same.