The present disclosure provides a CAR comprising a tumor antigen binding domain, a transmembrane domain, and an intracellular domain comprising an intracellular signaling domain of an interleukin-9 receptor alpha (IL9Ra), and modified cell(s), i.e., immune cell(s) or precursor cell(s) thereof, engineered to express the CAR. Also provided are methods and uses of the modified cells, e.g., for treating at least one sign and/or symptom of cancer. Related nucleic acids, vectors, and pharmaceutical compositions are also provided.

The present invention provides improved and/or shortened processes and methods for reprogramming TILs in order to prepare therapeutic populations of TILs with increased therapeutic efficacy. Such reprogrammed TILs find use in therapeutic treatment regimens.

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.

Methods for developing engineered T-cells for immunotherapy that are both non-alloreactive and resistant to immunosuppressive drugs. The present invention relates to methods for modifying T-cells by inactivating both genes encoding target for an immunosuppressive agent and T-cell receptor, in particular genes encoding CD52 and TCR. This method involves the use of specific rare cutting endonucleases, in particular TALE-nucleases (TAL effector endonuclease) and polynucleotides encoding such polypeptides, to precisely target a selection of key genes in T-cells, which are available from donors or from culture of primary cells. The invention opens the way to standard and affordable adoptive immunotherapy strategies for treating cancer and viral infections.

The invention is directed to modified T cells, methods of making and using isolated, modified T cells, and methods of using these isolated, modified T cells to address diseases and disorders. In one embodiment, this invention broadly relates to TCR-deficient T cells, isolated populations thereof, and compositions comprising the same. In another embodiment of the invention, these TCR-deficient T cells are designed to express a functional non-TCR receptor. The invention also pertains to methods of making said TCR-deficient T cells, and methods of reducing or ameliorating, or preventing or treating, diseases and disorders using said TCR-deficient T cells, populations thereof, or compositions comprising the same.

A composition for culturing peripheral blood monocyte-derived regulatory T cells includes at least one antibody selected from the group consisting of anti-CD2, anti-CD3, anti-CD7, anti-CD8, anti-CD28, anti-CD30L, anti-CD40, anti-CD70, anti-CD80, anti-CD83, and anti-CD86; at least one cytokine selected from the group consisting of interleukin-2, interleukin-4, interleukin-7, interleukin-12, interleukin-15, interleukin-34, and TGF-β; and superoxide dismutase. A regulatory T cell culturing method using this composition is also provided. The regulatory T cells according obtained by this method can be utilized for treatment of autoimmune diseases.

There is provided herein a method for expanding human CD4.sup.−CD8.sup.− regulatory T cells (DN Tregs) from a population of cells comprising DN Tregs, comprising: culturing the population of cells with artificial antigen presenting cells (APCs), preferably the DN Tregs are αβ-TCR.sup.+CD56.sup.− or alternatively γδ-TCR+.

The present invention relates to, inter alia, an engineered cell (e.g., iPSC, IPS-derived NK, or NK cell) comprising a disrupted B2M gene and an inserted polynucleotide encoding one or more of SERPINB9, a fusion of IL15 and IL15Rα, and/or HLA-E. The engineered cell can further comprise a disrupted CIITA gene and an inserted polynucleotide encoding a CAR, wherein the CAR can be an anti-BCMA CAR or an anti-CD30 CAR. The engineered cell may further comprise a disrupted ADAM17 gene, a disrupted FAS gene, a disrupted CISH gene, and/or a disrupted REGNASE-1 gene. Methods for producing the engineered cells are also provided, and therapeutic uses of the engineered cells are also described. Guide RNA sequences targeting described target sequences are also described.

The present invention relates to a method for inducing and proliferating target virus antigen-specific dual activated T cells, and can produce target virus antigen-specific dual activated T cells by treating monocytes, which are isolated from peripheral blood, with a cytokine and a virus antigen peptide mixture and culturing the same.

Methods and compositions for delivering a payload at TnMUC1 positive cancer cells. Anti-TnMUC1 CARs and transgene payloads can be engineered into immune cells so that the transgene payload is expressed and delivered at desired times from the immune cell. Such anti-TnMUC1 CAR T-cells with transgene payloads can be combined with the administration of other molecules, e.g., other therapeutics such as anticancer therapies.