Disclosed is a method of culturing natural killer cells (NK cells) applied to immunotherapy. More specifically, disclosed are a kit containing a medium for culturing NK cells (NKCM kit) that can efficiently amplify and activate NK cells effective for the treatment of malignant tumors by culturing lymphocytes derived from human peripheral blood, and a method of culturing natural killer cells using the kit. The method for amplifying NK cells of the present invention includes stimulating NK cells with lymphocytes separated from peripheral blood, culturing the NK cells in a medium containing IL-2, IL-12, IL-15, IL-17, IL-18, and IL-21, and isolating the NK cells. Provided is a pharmaceutical composition for cell therapy containing NK cells produced by the method of amplifying NK cells. The pharmaceutical composition for cell therapy is expected to be widely used to treat infections and/or cancer.

The present disclosure relates to a novel platform for immunotherapy which combines CAR engineered γδ T cells with armoring interleukin IL-18 that can be expressed constitutively or inducibly, or with a chimeric cytokine receptor comprising the endodomain of the IL-18 receptor. The system/platform and the associated methods according to the present disclosure have advantages such as increased immune cell potency and persistence for therapeutic applications.

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 a chimeric costimulatory antigen receptor (CoStAR) useful in adoptive cell therapy (ACT), and cells comprising the CoStAR. The CoStAR can act as a modulator of cellular activity enhancing responses to defined antigens. The present invention also provides CoStAR proteins, nucleic acids encoding the CoStAR and therapeutic uses thereof.

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 is targeted towards reinvigorating exhausted Tumor Infiltrating Lymphocytes (TILs) in vitro by co-culturing excised TIL containing tumor fragments with checkpoint inhibitors, stimulating the TILs with other interleukins known to revert T cell exhaustion), and/or inhibiting the effect of regulatory T cells secreted factors (such as IL-10) thereby creating a favorable tumor microenvironment (TME) where exhausted T-cells can expand faster and to higher numbers than currently established TIL expansion protocols.

Provided herein are cells engineered to have improved protection against natural killer cell killing. The cells are engineered to comprise an insertion of a polynucleotide encoding SERPINB9. Also provided herein are methods of making the engineered cells and therapeutic uses of the engineered cells. The engineered cells can also comprise at least one genetic modification within or near at least one gene that encodes one or more MHC-I or MHC-II human leukocyte antigens or component or transcriptional regulator of the MHC-I or MHC-II complex, at least one genetic modification that increases the expression of at least one polynucleotide that encodes a tolerogenic factor, and optionally at least one genetic modification that increases or decreases the expression of at least one gene that encodes a survival factor. The engineered cells can be stem cells and the engineered stem cells can be differentiated into various lineages having protection against NK cell killing.

Embodiments herein described provide antigen-presenting cell-mimetic scaffolds (APC-MS) and use of such scaffolds to manipulating T-cells. More specifically, the scaffolds are useful for promoting growth, division, differentiation, expansion, proliferation, activity, viability, exhaustion, anergy, quiescence, apoptosis, or death of T-cells in various settings, e.g., in vitro, ex vivo, or in vivo. Embodiments described herein further relate to pharmaceutical compositions, kits, and packages containing such scaffolds. Additional embodiments relate to methods for making the scaffolds, compositions, and kits/packages. Also described herein are methods for using the scaffolds, compositions, and/or kits in the diagnosis or therapy of diseases such as cancers, immunodeficiency disorders, and/or autoimmune disorders.

The present invention relates to chimeric antigen receptor cells targeting ROBO1, in particular, enhanced CAR-T cells and CAR-NK cells targeting ROBO1, and preparation and application thereof. The cells can stably expressing CAR elements, while secreting extracellular domain molecules expressing PD-1 protein or mutants thereof, and thus may block PD-11PD-L1 molecular interaction. It has been found through animal experiments that the cells have very good anti-tumor effects, and the above-mentioned cells can significantly reduce tumor recurrence and improve the survival rate compared with the conventional ROBO1-targeted CAR modified cells.

The present disclosure relates to expansion and activation of T cells. In an aspect, the present disclosure relates to expansion and activation of γδ T cells that may be used for transgene expression. In another aspect, the disclosure relates to expansion and activation of γδ T cells while depleting α- and/or β-TCR positive cells. T cell populations comprising expanded γδ T cell and depleted or reduced α- and/or β-TCR positive cells are also provided for by the instant disclosure. The disclosure further provides for methods of using the disclosed T cell populations.