Genonie-edited primary B cells, methods of making genome-edited primary B cells, a therapeutic cassette that can be introduced into primary B cells, and methods of using the genome-edited primary B cells and the therapeutic cassette.

The invention relates to induced pluripotent stem cells (iPSCs) produced from source dendritic cells (DCs). The invention also relates to synthetic DCs re-differentiated the iPSCs and which display a definitive adult phenotype rather than a primitive fetal/neonatal phenotype. The invention also relates to methods for making and methods of using the iPSCs and DCs of the invention.

The present disclosure relates to compositions, nucleic acid constructs, methods and kits thereof for cell induction or reprogramming cells to the dendritic cell state or antigen presenting cell state, based, in part, on the surprisingly effect described herein of novel use and combinations of transcription factors that permit induction or reprogramming of differentiated or undifferentiated cells into dendritic cells or antigen presenting cells. Such compositions, nucleic acid constructs, methods and kits can be used for inducing dendritic cells in vitro, ex vivo, or in vivo, and these induced dendritic cells or antigen presenting cells can be used for immunotherapy applications.

Provided herein are, inter alia, methods, compositions, and kits for producing adipocyte populations such as beige adipocyte populations. Also included are methods and compositions for increasing the level of adipocyte populations (e.g., beige adipocyte populations) in a subject, as well as methods and compositions for treating subjects who are overweight, obese, or who have diabetes.

The disclosure relates to methods of culturing and expanding CD4+ and/or CD8+ T cells in culture. In some embodiments, the methods include expanding, proliferating and storing lymphocytes in tissue culture by exposing the lymphocytes to a combination of cytokines and/or nucleic acids expressing cytokines or functional fragments or variants thereof. The disclosure further relates to methods of generating and manufacturing CD4+ and/or CD8+ T cells that are specific to one or a plurality of viral antigens.

An in vitro expansion process for rapid expansion of antigen specific T cells, such as allogeneic antigen specific cells comprising the steps culturing in a gas permeable vessel a population of PBMCs (such as allogeneic PBMCs) in the presence of antigen, for example a peptide or peptide mix relevant to a target antigen(s), in the presence of an exogenous cytokine characterized in that the expansion to provide the desired population of T cells is 14 days or less, for example 9, 10, 11 or 12 days, such as 10 days. The disclosure also extends to T cell populations generated by and obtained from the method and the use of same in therapy.

Embodiments of the disclosure concern multi-respiratory vims specific T cell lines and methods of using the same to treat and prevent viral infections.

Cell-based compositions and methods for targeting and treating human diseases, including cancers and infectious diseases, are provided, wherein exogenous intracellular sarcosine is used for improved delivery of the composition.

The invention involves generating a T cell response to subdominant antigens and using the cells to therapeutically change the cellular homeostasis and nature of the immune response. In a preferred embodiment, the cells are generated outside of the patient avoiding the influence of the patient's immunologic milieu. By stimulating and growing the T cells from a patient in a tissue culture to one or more subdominant antigens and the transplanting them into the patient, if enough cells are expanded and transplanted, the transplanted cells overwhelm the endogenous dominant T cells in the response to either break or induce immune tolerance or otherwise modify the immune response to the cells or organism expressing that antigen. When the memory cells are established they are then reflective of this new immunodominance hierarchy so that the desired therapeutic effect is long lasting. In effect, the transplantation exogenously generated T cells reactive to the subdominant antigens is recapitulating priming and rebalancing the patient's immune response to target previously subdominant antigens in the cells or organism to produce a therapeutic benefit.

The present invention concerns compositions and methods related to approaches to render ineffective Th1 T cells resistant to the inhibitory cytokine milieu present in a cancer microenvironment. In particular embodiments, tumor-specific T cells are modified to employ a chimeric receptor that binds inhibitory/suppressive cytokines and converts their intracellular consequences to a Th1 immunostimulaotyr/activating signal. In specific embodiments, the T cells employ a chimeric antigen receptor having exodomains for IL10, IL13 and/or IL4 fused with the signal transducing endodomains for IL2 and/or IL7.