Provided herein are constitutively active chimeric cytokine receptors (CACCRs). When present on chimeric antigen receptor (CAR)-bearing immune cells, such CACCRs allow for increased immune cell activation, proliferation, persistence, and/or potency. Also provided are methods of making and using the CACCRs described herein.

This disclosure relates to methods and systems for generating T cell precursors from hematopoietic stem and progenitor cells (HSPCs) in vitro. This disclosure discloses thatbesides activation of the Notch signaling pathwayactivation of tumor necrosis factor receptor 2 (TNFR2) present on the HSPCs is crucial to maximize the generation of T cell precursors. Hence, this disclosure relates to methods and systems, such as artificial thymic organoid systems, wherein agonists for TNFR2, such as transmembrane tumor necrosis factor (tmTNF), are used to maximally generate T cell precursors. The latter T cell precursors are useful for immune reconstitution due to transplantation or immunodeficiency disorders and may be used to generate off-the-shelf chimeric antigen receptor T cells or T cell receptor engineered T cells for immunotherapeutic purposes.

Provided are NK-92 cells expressing a chimeric antigen receptor (CAR). The CAR can comprise an intracellular domain of Fc?RI?. Also described are methods for treating a patient having or suspected of having a disease that is treatable with NK-92 cells, such as cancer or a viral infection, comprising administering to the patient NK-92-CAR cells.

The invention provides improved compositions and methods for the treatment of solid cancers.

Provided here are engineered immune cells that comprise a constitutively active chimeric cytokine receptor (CACCR) and a B-cell maturation antigen (BCMA) specific chimeric antigen receptor (CAR). Also provided herein are engineered immune cells that comprise one or more nucleic acids e.g. a bicistronic vector such as a viral vector that encode the CACCRs and BCMA CARs and engineered immune cells e.g. engineered autologous or allogeneic T cells that express both CACCRs and BCMA CARs from the nucleic acids. When present on chimeric antigen receptor (CAR)-bearing engineered immune cells, the CACCRs allow for increased immune cell activation, proliferation, persistence, and/or potency. Further provided herein are methods of making and using the engineered immune cells described herein, such as methods of treating a disease or condition by administering at least one appropriate dose of the cells to a patient suffering from the condition.

The present invention is directed to genome editing systems, reagents and methods for immunooncology.

Compounds that either produce a higher proportion or greater absolute number of phenotypically identified naive, stem cell memory, central memory T cells, adaptive NK cells, and type I NKT cells are identified. Compositions and methods for modulating immune cells including T, NK, and NKT cells for adoptive cell therapies, such as those providing improvements in one or more therapeutic outcomes, are provided.

The presently disclosed subject matter provides methods and compositions for enhancing the immune response toward cancers and pathogens. It relates to novel designs of T cell receptors (TCRs) and engineered immunoresponsive cells comprising the same. The novel TCR binds to an antigen in an HLA-independent manner. In certain embodiments, the novel TCR provides enhanced sensitivity for a target gene having a low expression level.

An immunoresponsive cell, such as a T-cell expressing a second generation chimeric antigen receptor comprising: (a) a signalling region; (b) a co-stimulatory signalling region; (c) a transmembrane domain; and (d) a binding element that specifically interacts with a first epitope on a target antigen; and a chimeric costimulatory receptor comprising (e) a co-stimulatory signalling region which is different to that of (b); (f) a transmembrane domain; and g) a binding element that specifically interacts with a second epitope on a target antigen.

This arrangement is referred to as parallel chimeric activating receptors (pCAR). Cells of this type are useful in therapy, and kits and methods for using them as well as methods for preparing them are described and claimed.

An engineered immune cell for immunotherapy, which has a relatively high persistence and/or survival rate of transplantation in a host organism, and a preparation method therefor.