Compositions disclosed herein, and methods of use thereof included those for treating or preventing sepsis in a subject in need, including methods of extending of the survival of a subject suffering from sepsis, and reduction of organ dysfunction or failure due to sepsis. Methods of treating or preventing sepsis in a subject in need includes administering compositions comprising early apoptotic cells or early apoptotic cell supernatants. Compositions and methods of use thereof may reduce the negative proinflammatory effect accompanying sepsis. In certain instances, compositions may include additional agents.

The present disclosure relates to cells capable of co-expressing T cell receptors (TCR) together with membrane-bound IL-15 polypeptides and/or CD8 polypeptides and the use thereof in adoptive cellular therapy. The present disclosure further provides for modified IL-15, IL-15R, IL-15/IL-15R fusion polypeptide, and IL-15R/IL-15 fusion polypeptide sequences, vectors, and associated methods of making and using the same. The present disclosure further provides for modified CD8 sequences, vectors, and associated methods of making and using the same.

Variant IL2RG (CD132 or common- or c) chains are provided that are capable of rendering cells responsive to variant cytokines.

The present disclosure generally relates to, inter alia, a class of chimeric switch receptors containing an endodomain of an IL-9 receptor, engineered to modulate transcriptional regulation in a ligand-dependent manner. The disclosure also provides compositions and methods useful for producing such receptors, nucleic acids encoding same, host cells genetically modified with the nucleic acids, as well as methods for modulating gene expression, modulating an activity of a cell, and/or for the treatment of various health conditions or diseases.

Anti-IL13Ra2 antibodies and antigen-binding fragments thereof are described. Also described are nucleic acids encoding the antibodies, compositions comprising the antibodies, and methods of producing the antibodies and using the antibodies for treating or preventing diseases such as cancer, inflammatory disease, and/or autoimmune disease.

D domain (DD) containing polypeptides (DDpp) that specifically bind targets of interest (e.g., BCMA, CD123, CS1, HER2, AFP, and AFP p26) are provided, as are nucleic acids encoding the DDpp, vectors containing the nucleic acids and host cells containing the nucleic acids and vectors. DDpp such as DDpp fusion proteins, are also provided as are methods of making and using the DDpp. Such uses include, but are not limited to diagnostic and therapeutic applications.

Natural killer (NK) cells are innate lymphocytes with cancer and viral immunosurveillance capabilities. Prior studies have established that human and mouse NK cells can acquire features of adaptive immunity, demonstrating immunological memory-like properties. Memory-like NK cells have been described in response to infection with cytomegalovirus in humans and mice, representing antigen-specific memory NK cells. NK cells, designated as cytokine-induced memory-like NK cells, with adaptive immune cell features can be generated in vitro and used in clinical trials in human cancer patients. Chimeric transmembrane receptor polypeptides expressed in natural killer cells or T-cells, are provided.

Immunoresponsive cells comprising an NKG2D polypeptide and a CXCR2 polypeptide, and, optionally, a fusion polypeptide comprising a DNAX-activating 10 (DAP10) polypeptide and a DNAX-activating protein 12 (DAP12) polypeptide, are provided. Also provided are methods of making and using such immunoresponsive cells.

Adoptive T-cell therapy has shown tantalizing promise as a cancer treatment strategy, with several clinical trials reporting that T cells expressing chimeric antigen receptors (CARs) can eradicate tumors in patients with relapsed disease. However, CAR-T cells rely on receptor-mediated recognition of surface-bound antigens that are seldom tumor-exclusive, resulting in severe on-target, off-tumor toxicities that have led to patient deaths in clinical trials. There is a growing consensus that the lack of suitable antigens poses a major obstacle to the broad application of engineered tumor-targeting T cells. The ability to overcome T cells' reliance on surface antigen presentation and interrogate intracellular disease signatures would significantly expand the pool of detectable tumor markers and improve tumor-targeting specificity. Here, we present a novel strategy to reprogram T-cell-mediated cytotoxicity to interrogate intracellular disease signatures. We have engineered a switchable form of the cytotoxic protein Granzyme B (GrB) that is produced and delivered by T cells into target cells, but becomes active if and only if a tumor-associated protease is present inside the target cell. As a proof of concept, we have developed a GrB switch that responds to Sentrin-specific protease 1 (SENP1), an oncoprotein known to be overexpressed in prostate, pancreatic, and thyroid oncocytic tumor cells. We demonstrate that this GrB switch, termed cytoplasmic oncoprotein verification evaluator and response trigger (COVERT), is efficiently expressed and packaged by human T cells and properly trafficked to the immunological synapse between T cells and target cells. Furthermore, we show that COVERT is produced as an enzymatically inert protein that is activated by SENP1 in a dose-dependent manner. Finally, we describe designs to adapt COVERT into a modular platform technology that will expand the repertoire of candidate target antigens. We envision that COVERT can be utilized in combination with existing CAR technology to improve the tumor-targeting precision of cell-based immunotherapy.

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Genetically engineered hematopoietic cells such as hematopoietic stem cells having one or more genetically edited genes of cell-surface proteins and therapeutic uses thereof, either alone or in combination with immune therapy that targets the cell-surface protein(s).