The present invention provides, in certain aspects, a natural killer (NK) cell that expresses all or a functional portion of interleukin-15 (IL-15), and methods for producing such cells. The invention further provides methods of using a natural killer (NK) cell that expresses all or a functional portion of interleukin-15 (IL-15) to treat cancer in a subject or to enhance expansion and/or survival of NK cells.

Embodiments of the present disclosure relate to compositions and methods of enhancing lymphocytes' ability to treat cancer patients. Embodiments relate to a polynucleotide comprising a nucleic acid encoding a chimeric antigen receptor (CAR), a nucleic acid encoding an Oxygen-Dependent Degradation domain (ODD), and a nucleic acid encoding one or multiple sequences of Hypoxia-Response Element (HRE).

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.

Disclosed herein are methods of cancer treatment comprising administration of a natural killer (NK) cell or cell line in combination with an IL-6 antagonist, such as an antibody to IL-6 or its receptor, especially for treatment of cancer expressing IL-6 receptors and in which checkpoint inhibitory receptors, such as PDL-1 and/or PDL-2 are expressed/upregulated during disease.

Anti-IL-12/IL-23p40 antibodies, such as ustekinumab, are used in methods and compositions for safe and effective treatment of psoriasis, particularly moderate to severe chronic plaque psoriasis, in pediatric patients. The methods and compositions address a clear unmet medical need in this patient population.

The present invention relates, inter alia, to compositions and methods, including heterodimeric proteins that find use in the treatment of disease, such as immunotherapies for cancer and autoimmunity.

The present invention relates, inter alia, to compositions and methods, including heterodimeric proteins that find use in the treatment of disease, such as immunotherapies for cancer and autoimmunity.

The present disclosure relates extracellular vesicles, e.g., exosomes, comprising an antigen-binding moeity, e.g., a single-domain antigen-binding moeity, e.g., a vNAR, a VHH, or a fragment thereof, that specifically binds transferrin receptor, and methods of making and using the same.

Provided are various embodiments relating to compositions and methods for treating vascular disease, including core NOX1 promoters and variants thereof for regulating expression of transgenes in response to vascular pathology and allowing for increased transgene loading capacity. Also provided are variant FOXP polypeptides having a zinc finger and leucine zipper region of a different FOXP polypeptide. Further provided are vectors comprising the core NOX1 promoters and/or a coding sequence for variant FOXP polypeptides described herein and optionally coding sequence(s) for one or more additional therapeutic polypeptide(s), such as IL10, for treating inflammation-associated diseases, such as vascular disease. Also provided is a screening model for testing therapeutic agents capable of treating established and ongoing atherosclerotic pathology.

The present disclosure relates generally to compositions and methods for modulating signal transduction mediated by interleukin-12 and interleukin-23. In particular, the disclosure provides novel variants of interleukin-12 subunit p40 with reduced binding affinity to IL-12Rβ1. Also provided are compositions and methods useful for producing such IL-12p40 polypeptide variants, as well as methods for modulating IL-12p40-mediated signaling, and/or for the treatment of conditions associated with perturbations of signal transduction mediated by IL-12p40.