The present disclosure provides recombinant T cells that include a vector encoding one or more of peroxisome proliferator-activated receptor (PPAR) gamma coactivator 1-alpha (PGC1α), mitochondrial transcription factor A (Tfam), GA binding protein transcription factor alpha subunit (GABPA), and estrogen-related receptor alpha (ERRα). Such recombinant T cells can also include a chimeric antigen receptor (CAR) or a recombinant T cell receptor (TCR). Methods of using these recombinant T cells in cancer immunotherapy are provided. Also provided are kits and compositions that can be used with such methods.

Provided herein are methods for ex vivo expansion of a T cells, including tumor-reactive T cells, and compositions containing such T cells. Also provided are methods for treating diseases and conditions such as cancer using compositions of the present disclosure.

Provided are methods of producing an isolated population of T cells for adoptive cell therapy. Also provided are related isolated populations of cells, pharmaceutical compositions, and methods of treating or preventing cancer, infections, and autoimmune conditions in a patient.

Provided herein are methods and customized media compositions for culturing CIK NKT cells.

Disclosed are compositions and methods for targeted treatment of infections and cancers expressing cancers. In particular, tumor infiltrating lymphocytes (TILs) are identified that can be used with adoptive cell transfer to target, penetrate, and kill solid tumor masses. Therefore, also disclosed are methods of providing an immunotherapy in a subject with an infection or cancer that involves adoptive transfer of the disclosed TILs.

Methods of generating definitive hematopoietic cells from source cells including at least one of: differentiating iPS cells, cells directly reprogrammed to pre-cursors of hematopoietic cells, cells directly reprogrammed to definitive hematopoietic cells, and adult or neonatal hematopoietic cells from bone marrow, cord blood, placenta, or mobilized peripheral blood, the method including using a metabolic regulator to activate a tricarboxylic acid cycle of the source cells. Other methods relate to generating primitive hematopoietic cells from source cells including at least one of: differentiating iPS cells, cells directly reprogrammed to pre-cursors of hematopoietic cells, cells directly reprogrammed to definitive hematopoietic cells, and adult or neonatal hematopoietic cells from bone marrow, cord blood, placenta, or mobilized peripheral blood, the method including using a metabolic regulator to inhibit a tricarboxylic acid cycle of the source cells. Some aspects relate to a metabolic regulator for activation of a tricarboxylic acid cycle of source cells for the production of definitive or primitive hematopoietic cells.

The disclosure features methods and compositions for differentiating stem cells into hematopoietic stem and progenitor cells (HSPC) and/or Natural Killer (NK) cells. The methods and compositions described herein are used to differentiate stem or progenitor cells having at least one gene-edit that is maintained in the differentiated cell. Also provided are differentiated cells produced using the methods and compositions described herein for therapeutic applications.

A method for producing an engineered T cell population includes obtaining a cell population containing a monocyte and a T cell, resting the obtained cell population on a surface, adhering the monocyte to the surface, retaining a non-adherent cell population, activating the non-adherent cell population, introducing a nucleic acid into the activated non-adherent cell population to obtain a transformed T cell, and expanding the transformed T cell to obtain the engineered T cell population.

The invention provides improved T cell compositions and methods for manufacturing T cells. More particularly, the invention provides methods of T cell manufacturing that result in adoptive T cell immunotherapies with improved survival, expansion, and persistence in vivo.

The present invention relates to the field of medicine, specifically the field of treatment of cancer. More specifically, the invention relates to a method for the ex vivo production of a population of highly functional NK cells from CD34-positive cells, to a population of highly functional NK cells obtained and to the use of such population of highly functional NK cells for adoptive cell therapy.