Embodiments herein relate to in vitro production methods of hematopoietic stem cell (HSC) and hematopoietic stem and progenitor cell (HSPC) that have long-term multilineage hematopoiesis potentials upon in vivo engraftment. The HSC and HSPCs are derived from pluripotent stem cells-derived hemogenic endothelia cells (HE) by non-integrative episomal vectors-based gene transfer.

The invention provides culture platforms, cell media, and methods of differentiating pluriptent cells into hematopoietic cells. The invention further provides pluripotent stem cell-derived hematopoietic cells generated using the culture platforms and ethods disclosed herein, which enable feed-free, monolayer culturing and in the absence of EB formation. Specifically, pluripotent stem cell-derived hematopoietic cell of this invention include, and not limited to, iHSC, definitive hemogenic endothelium, hematopoietic multipotent progenitors, T cell progenitors, NK cell progenitors, T cells, and NK cells.

The present invention relates to the field of manufacturing of Natural Killer (NK) Cells genetically modified with viral vectors carrying a polynucleotide coding for a Chimeric Antigen Receptors (CARs). The present invention further relates to CAR-NK cells obtained with the method and use of the CAR-NK cells in medicine, in particular for use in a method of treating cancer.

This invention relates to Natural Killer (NK) cell populations, to methods of producing the same and therapeutic applications thereof. More specifically, the invention relates to the expansion of NK cells by increasing the expression of specific transcription factors associated with NK cell production.

The present disclosure relates generally to culture media formulations and culture methods. More particularly, the present disclosure provides defined serum-free culture media, kits and methods for generating progenitor T cells and derivatives thereof, including mature T cells. The present disclosure further provides the cells generated using the media, kits and methods, as well as methods of treatment using the generated cells.

A method for arterial endothelial-enhanced functional T cell generation is provided. In the method, arterial endothelial cells enhance functional T cell generation by promoting the generation of hematopoietic progenitor cells with T-lineage bias. The first stage of T cell differentiation from human pluripotent stem cells (hPSCs) is optimized, and it is found that hPSC-derived autologous arterial endothelial cells increase the T cell potential of hematopoietic progenitor cells. Moreover, the T cells generated by arterial endothelial cell priming share similar function to that of human peripheral blood T cells. hPSC-derived CD19-CAR-T cells have been verified to have tumor-killing effects both in vivo and in vitro. The established hPSC-T differentiation system would provide a valuable resource for chimeric antigen receptor T cell (CAR-T) therapy.

According to the present disclosure, provided is a method for manufacturing induced pluripotent stem cells including preparing cells and introducing RNA into the cells, wherein the RNA includes RNA encoding a reprogramming factor and wherein, in the RNA introduced into the cells, double-stranded RNA is substantially removed.

Embodiments herein relate to in vitro production methods of hematopoietic stem cell (HSC) and hematopoietic stem and progenitor cell (HSPC) that have long-term multilineage hematopoiesis potentials upon in vivo engraftment. The HSC and HSPCs are derived from pluripotent stem cells-derived hemogenic endothelia cells (HE) by non-integrative episomal vectors-based gene transfer.

The present invention provides a cell population and a method of obtaining the same. The cell population of the present invention is obtained by culturing mononuclear cells derived from bone marrow, umbilical cord blood, or peripheral blood in a medium containing serum and four or less of factors selected from the group consisting of stem cell factor, interleukin-6, FMS-like tyrosine kinase 3 ligand, thrombopoietin, and vascular endothelial growth factor.

Modified natural killer (NK) or T cells expressing hematopoietic growth factor receptors are provided. In some embodiments, the NK cells or T cells express a thrombopoietin receptor or an erythropoietin receptor. Methods of treating a subject with cancer are also provided, including administering the modified NK cells or T cells to the subject in combination with a thrombopoietin receptor agonist or erythropoietin receptor agonist, and in some example, interleukin-2, particularly reduced or low-dose amounts of IL-2.