Abstract: In one aspect, the invention relates to substituted 1-phenyl-3-(piperidin-4-yl)urea analogs, derivatives thereof, and related compounds, which are useful as inhibitors of the DCN1-UBC12 interaction inhibitors of DCN1-mediated cullin-RING ligase activity, methods of making same, pharmaceutical compositions comprising same, methods of treating disorders using the disclosed compounds and compositions, methods of treating disorders associated with a DCN1-UBC12 interaction dysfunction, methods of treating disorders associated with a DCN1-mediated cullin-RING ligase activity dysfunction, methods of male contraception comprising the disclosed compounds and compositions, and kits comprising the disclosed compounds and compositions. 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: 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.

Abstract: In one aspect, a method of treating a subject having or at risk of having graft-versus-host disease (GvHD) generally includes administering to the subject a plurality of myeloid-derived suppressor cells (MDSCs) effective to ameliorate at least one symptom or clinical sign of graft-versus-host disease compared to a suitable control subject. In another aspect, a method of treating a tumor in a subject generally includes administering to the subject an anti-tumor therapy and co-administering to the subject an inflammasome inciting agent in an amount effective to increase inflammasome activation of MDSCs sufficiently to reduce suppressor function of the MDSCs.

Abstract: A method of identifying a lead or candidate compound that modulates the activity of GTPase-Activating Protein SH3 Domain-Binding Proteins (G3BP) is provided, which includes determining whether a compound modulates the interaction between the N-terminal Nuclear Transport Factor 2-like (NTF2L) domain of G3BP and FGDF peptide of ubiquitin specific protease 10 (USP10) or non-structural protein 3 (nsP3).

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 encompasses 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: 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 encompasses 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: In one aspect, the invention relates to substituted urea depsipeptide analogs, derivatives thereof, and related compounds, which are useful as activators the ClpP endopeptidease; synthesis methods for making the compounds; pharmaceutical compositions comprising the compounds; and methods of treating infectious disease using the compounds and compositions. 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 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 encompasses 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: There is provided a nucleic acid molecule comprising a nucleotide sequence encoding a Factor VIII protein, wherein a B domain portion of the Factor VIII protein is encoded by a nucleotide sequence between 90 and 111 nucleotides in length and has an amino acid sequence that is at least 85% identical to SEQ ID NO: 4 which comprises six asparagine residues. Also provided is a Factor VIII protein, a vector comprising the above nucleic acid molecule, a host cell, a transgenic animal, a method of treating Haemophilia Haemophilia A, and a method for the preparation of a parvoviral gene delivery vector.

Abstract: Anti-CD223 antibodies overcome immune suppression in cancer patients. The anti-CD223 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 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 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 encompasses 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: An optimized coding sequence of human blood clotting factor eight (VIII) and a promoter may be used in vectors, such as rAAV, for introduction of factor VIII, and/or other blood clotting factors and transgenes. Exemplary of these factors and transgenes arc alpha-1-antitrypsin, as well as those involved in the coagulation cascade, hepatocye biology, lysosomal storage, urea cycle disorders, and lipid storage diseases. Cells, vectors, proteins, and glycoproteins produced by cells transformed by the vectors and sequence, may be used in treatment.

Abstract: The invention is directed to a method for improving learning and/or memory (e.g., auditory, visual, somatosensory or motor) in adults and children of an age which is beyond the early critical period for learning, said method comprising inhibiting (i) ecto-5?-nucleotidase (Nt5e, aka CD73) or (ii) A1 adenosine receptor (A1R, aka Adora1) expression or function in the brain. The invention is also directed to a method for treating learning and memory defects and neurological diseases associated with an abnormal auditory, visual, or somatosensory perception by inhibiting Nt5e or A1R expression or function in the brain.

Abstract: In one aspect, the invention relates to substituted urea depsipeptide analogs, derivatives thereof, and related compounds, which are useful as activators the C1pP endopeptidease; synthesis methods for making the compounds; pharmaceutical compositions comprising the compounds; and methods of treating infectious disease using the compounds and compositions. 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 compounds of the invention are antagonists of MDM2 and MDMX, with excellent specificity for MDM2 and MDMX over other proteins, and with selective binding affinity to MDMX over MDM2. The compounds can therefore regulate p53 activity and treat a variety of cancers. 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: A modified effector cell includes a non-reversibly produced vector-encoded anti-GD2-BB-? chimeric receptor for use in disialoganglioside GD2-expressing neoplasia, which is inserted in the cell, to obtain an effector cell that stably produces the anti-GD2-BB-? chimeric receptor, the chimeric receptor having two distinct mutually fused portions, i.e. an intra-cytoplasmic portion and an extra-cytoplasmic portion.