The present application provides methods and devices for the production and recovery of cell aggregates. In one embodiment, the device is a microwell device with a high density of microwells. The application also provides a device for extracting cell aggregates such as stem cells or embryoid bodies from well plates. Such cell aggregates are used for the differentiation of pluripotent stem cells such as embryonic stem cells, in the fields of developmental biology and regenerative medicine/tissue engineering.

The present invention relates to methods for developing engineered immune cells such as T-cells for immunotherapy that have a higher potential of persistence and/or engraftment in host organism. IN particular, this method involves an inactivation of at least one gene involved in self/non self recognition, combined with a step of contact with at least one non-endogenous immunosuppressive polypeptide. The invention allows the possibility for a standard and affordable adoptive immunotherapy, whereby the risk of GvH is reduced.

Antiviral compounds, compositions and method are presented. The composition comprises a first antiviral compound and a second antiviral compound, as described herein, optionally a third antiviral compound, as described herein, and an excipient. The excipient may be pharmaceutically acceptable. The excipient may comprise at least one compound that does not occur naturally with a combination of antiviral compounds as described herein in nature. The method comprises administering a pharmaceutical composition comprising a combination of antiviral compounds as described herein and a pharmaceutically acceptable excipient to a patient who has, is suspected of having, or is susceptible to a viral infection.

Composition and methods for ex vivo expansion of natural killer (NK) cells, and methods for cell-based cancer immunotherapy are disclosed. Leukemic cell-derived dendritic cells and anti-PD-L1 antibodies, and certain embodiments with addition of PBMCs are used for in vivo administration for cancer treatment. Leukemic cell-derived dendritic cells and anti-PD-L1 antibodies are also used for ex vivo expansion of NK cells.

Genetically modified cells that are compatible with multiple subjects, e.g., universal donor cells, and methods of generating said genetic modified cells are provided herein. The universal donor cells comprise at least one genetic modification within or near at least one gene that encodes a survival factor, wherein the genetic modification comprises an insertion of a polynucleotide encoding a tolerogenic factor. The universal donor cells may further comprise at least one genetic modification within or near a gene that encodes one or more MHC-I or MHC-II human leukocyte antigens or a component or a transcriptional regulator of a MHC-I or MHC-II complex, wherein said genetic modification comprises an insertion of a polynucleotide encoding a second tolerogenic factor.

Provided is a method for inducing CD4.sup.−CD8.sup.+ T cells having an antigen specific cytotoxic activity from pluripotent stem cells, comprising the steps of: (1) differentiating pluripotent stem cells to give a cell culture comprising CD4.sup.−CD8.sup.− T cells and CD4.sup.+CD8.sup.+ T cells, (2) removing CD4.sup.−CD8.sup.− cells from the cell culture obtained in step (1), and (3) differentiating the CD4.sup.+CD8.sup.+ cells in the cell culture into CD4.sup.−CD8.sup.+ T cells.

Provided is a method for inducing CD4.sup.−CD8.sup.+ T cells having an antigen specific cytotoxic activity from pluripotent stem cells, comprising the steps of: (1) differentiating pluripotent stem cells to give a cell culture comprising CD4.sup.−CD8.sup.− T cells and CD4.sup.+CD8.sup.+ T cells, (2) removing CD4.sup.−CD8.sup.− cells from the cell culture obtained in step (1), and (3) differentiating the CD4.sup.+CD8.sup.+ cells in the cell culture into CD4.sup.−CD8.sup.+ T cells.

Provided are methods, uses, and articles of manufacture of combination therapies involving immunotherapies and cell therapies, such as adoptive cell therapy, e.g. a T cell therapy, and the use of an inhibitor of a prosurvival BCL2 family protein, e.g. a BCL2 inhibitor, for treating subjects having or suspected of having a cancer, and related methods, uses, and articles of manufacture. The T cell therapy includes cells that express recombinant receptors such as chimeric antigen receptors (CARs).

The present invention relates to compositions and methods for generating a modified T cell with a nucleic acid capable of downregulating endogenous gene expression selected from the group consisting of TCR α chain, TCR β chain, beta-2 microglobulin and FAS further comprising a nucleic acid encoding a modified T cell receptor (TCR) comprising affinity for a surface antigen on a target cell or an electroporated nucleic acid encoding a chimeric antigen receptor (CAR). Also included are methods and pharmaceutical compositions comprising the modified T cell for adoptive therapy and treating a condition, such as an autoimmune disease.

Methods of inducing thrombopoiesis and/or treating thrombocytopenia in a subject are provided. Accordingly there is provided a method comprising contacting stem cells with a differentiation potential towards platelets or hematopoietic progenitor cells derived therefrom with Livin, thereby inducing thrombopoiesis. Also provided is a method comprising contacting cells with a differentiation potential towards platelets with tLivin, thereby inducing thrombopoiesis. Also provided are compositions and isolated population of cells for inducing thrombopoiesis and/or treating thrombocytopenia in a subject.