Abstract: The present invention provides chimeric cytokine receptors, particularly chimeric cytokine receptors that canbe activated in tumor microenvironment, and their uses in tumor immunotherapy (e.g., adoptive cell therapy). The present invention further provides methods of genetically modifying therapeutic cells resulting in an enhanced immune response against a target antigen. The application further provides therapeutic cells that express said chimeric cytokine receptors and methods for treating patients using the modified therapeutic cells.

Abstract: 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.

Abstract: The present disclosure relates to methods of treating a coenzyme A reduction, elevation, sequestration, toxicity, or redistribution (CASTOR) disease such as, for example, defects in fatty acid oxidation enzymes, methylmalonic acidemia, glutaric acidemia, propionic academia, and HMG-CoA lyase, via small molecule modulators of CoA levels. This abstract is intended as a scanning tool for purposes of searching in the particular art and is not intended to be limiting of the present invention.

Abstract: The application provides T cell gene expression signatures that can be used to predict T cell therapy outcomes.

Abstract: Described is a method for treating a social memory deficit in a subject with a neuropsychiatric disease is treated by administering a peptide encoded by 2510002D24Rik or Atp23 genes, a vector expressing such peptide, or an agent capable of increasing the level or activity of such peptide. The method may be used to treat schizophrenia or autism. The peptide, vector or agent can be administered directly to the hippocampus, such as by transcranial surgical injection.

Abstract: The application relates to a chimeric antigen receptor that directly and/or indirectly targets cells and their uses in tumor immunotherapy. The application also relates to polynucleotides that encode the chimeric antigen receptor and optionally accessory genes, vectors, and host cells comprising the chimeric antigen receptor and optionally a second antigen targeting moiety (e.g., a second chimeric antigen receptor or a bispecific molecule). The application also relates to methods for preparing host cells comprising the chimeric antigen receptor and optionally the second antigen targeting moiety.

Abstract: The application provides modified immune effector cells wherein the DNA (cytosine-5)-methyltransferase 3A (DNMT3A)-mediated de novo DNA methylation of the cell genome is inhibited, and STAT5 signaling pathway is activated. The application also provides related pharmaceutical compositions and the methods for generating such modified immune effector cells. The application further provides uses of such modified immune effector cells for treating diseases such as cancers, infectious diseases and autoimmune diseases.

Abstract: The present application provides methods of enhancing T cell function (e.g., expansion, persistence and/or effector functions), particularly by genetic modification of the Regnase-1, Batf, and additional genes (alone or in combination). The application also provides modified T cells manufactured using the methods provided by this invention and related pharmaceutical compositions. The application further provides methods of using the modified T cells for treating a disease (e.g., a cancer or an infectious disease).

Abstract: The invention relates to a high-throughput method for characterizing the genome-wide activity of editing nucleases in vitro.

Abstract: The present disclosure provides chimeric antigen receptors (CARs), particularly CARs that have enhanced antitumor properties and/or can be regulated by safety switches. Also provided are polypeptides of the CARs and other related molecules, polynucleotides, vectors, and cell compositions comprising the same. Pharmaceutical compositions comprising the polypeptides, polynucleotides, vectors, or cells of the present disclosure, and their uses in treating a cancer in a subject are also provided.

Abstract: The invention is directed to methods of assessing the safety of therapeutic compounds and therapeutic genetic manipulations, including integrating gene therapy vectors and genome editing. In particular, the invention provides a method, wherein the oncogenic potential of therapeutic compounds and therapeutic genetic manipulations, including integrating gene therapy vectors and genome editing, is determined by determining the percentage of differentiation blocked hematopoietic progenitor cells.

Abstract: The present invention relates to nucleic acid molecules containing spacers and methods of using the same.

Abstract: The present invention relates to nucleic acid molecules containing spacers that can be packaged into viral particles and methods of producing them. In a first aspect, the invention features a nucleic acid molecule including a first spacer (SSI); a first inverted terminal repeat (ITR1); a cloning site (CS); a second inverted terminal repeat (ITR2); and a second spacer (SS2), such as a eukaryotic spacer; operably linked to each other in a 5?-to-3? direction as: SS1-ITR1-CS-ITR2-SS2. In an embodiment, the invention features a vector comprising any of the above-described nucleic acid molecules. In another aspect, the invention features a plurality of viral particles including the nucleic acid molecule. The invention further includes a host cell including any of the above-described vectors.

Abstract: The application relates to a chimeric antigen receptor that targets Eph receptors and allows activation of co-stimulatory pathways. The application also relates to polynucleotides that encode the chimeric antigen receptor, vectors, and host cells comprising the chimeric antigen receptor. The application also relates to methods for preparing host cells comprising a chimeric antigen receptor in order to improve the in vivo effector function of the chimeric antigen receptor host cells.

Abstract: This disclosure relates to the genetic modification of DNMT3A gene in immune cells. In certain embodiments, the modified immune cells may be used in adoptive T cells therapies to enhance immune responses against cancer or chronic infections. In certain embodiments, the disclosure relates to deleting, changing, or inserting nucleotides within the DNMT3A gene in immune cells, e.g., human CD8 T cells, such that the DNMT3A gene product does not function for methylation. In certain embodiments, modification of the DNMT3A gene provides an improvement in antigen-specific T cells functions and/or an enhancement of the longevity of the cells.

Abstract: The invention provides a chimeric receptor comprising NKG2D, DAP10 and CD3 zeta. Also disclosed is a composition comprising this chimeric receptor and methods for making and using it to enhance the cytotoxicity and antitumor capacity of NK cells. The invention also encompansses methods for use of NKG2D-DAP10-CD3 zeta polypeptides, vectors and cells in methods for treating cancer and other proliferative disorders, as well as infectious diseases.

Abstract: Combinations of anti-cancer antibodies and inhibitory antibodies to CD223 overcome immune suppression in cancer patients. The inhibitory antibodies may be generated in an animal by injection of fragments of CD223. Antibodies may be monoclonal antibodies or single chain antibodies or humanized antibodies.

Abstract: The invention relates to a high-throughput method for characterizing the genome-wide activity of editing nucleases in vitro.

Abstract: The application relates to a chimeric receptor that targets CD33 and allows activation of the co-stimulatory pathway without binding the natural ligand. The application also relates to polynucleotides that encode the chimeric receptor, vectors, and host cells comprising the chimeric receptor. The application also relates to methods for preparing host cells comprising a chimeric antigen receptor in order to improve the in vivo persistence of the chimeric antigen receptor host cells.

Abstract: The present disclosure relates to chemical compounds that modulate pantothenate kinase (PanK) activity for the treatment of metabolic disorders (such as diabetes mellitus type II), neurologic disorders (such as pantothenate kinase-associated neurodegeneration), pharmaceutical compositions containing such compounds, and their use in treatment. This abstract is intended as a scanning tool for purposes of searching in the particular art and is not intended to be limiting of the present invention.