Abstract: The present invention relates to the field of stem cell biology, in particular the linage specific differentiation of pluripotent or multipotent stem cells, which can include, but is not limited to, human embryonic stem cells (hESC), human induced pluripotent stem cells (hiPSC), somatic stem cells, cancer stem cells, or any other cell capable of lineage specific differentiation. Specifically described are methods to direct the lineage specific differentiation of hESC and/or hiPSC to nociceptors (i.e. nociceptor cells) using novel culture conditions. The nociceptors made using the methods of the present invention are further contemplated for various uses including, but limited to, use in in vitro drug discovery assays, pain research, and as a therapeutic to reverse disease of, or damage to, the peripheral nervous system (PNS). Further, compositions and methods are provided for producing melanocytes from human pluripotent stem cells for use in disease modeling.

Abstract: Disclosed herein are methods and compositions related to the treatment, prevention, and/or amelioration of cancer in a subject in need thereof. In particular aspects, the present technology relates to the use of poxviruses, including a recombinant modified vaccinia Ankara (MVA) virus or vaccinia virus with deletion of vaccinia host-range factor C7 (MVA?C7L and VACV?C7L, respectively), alone or in combination with immune checkpoint blocking agents, as an oncolytic and immunotherapeutic composition. In some embodiments, the technology of the present disclosure relates to a MVA?C7L or VACV?C7L virus further modified to express human Fms-like tyrosine kinase 3 ligand (Flt3L).

Abstract: The present disclosure provides antibodies that specifically bind to human OX40 receptor (OX40) and/or human GITR receptor (GITR), including multispecific antibodies that bind, e.g., to OX40 and GITR, and compositions comprising such antibodies. The antibodies disclosed herein modulate OX40 and/or GITR activity e.g., enhance, activate, induce, reduce, deactivate, or inhibit OX40 and/or GITR activity. The present disclosure also provides methods for treating disorders, such as cancer, autoimmune diseases or disorders, or inflammatory diseases or disorders, by administering an antibody that specifically binds to human OX40 and/or human GITR and modulates OX40 and/or GITR activity.

Abstract: The present disclosure provides methods for generating midbrain dopamine neurons (mDAs) and precursors thereof, mDAs and precursors thereof generated by such methods and compositions comprising such cells, and uses thereof for preventing and/or treating neurological disorders. The present disclosure further provides methods of isolating mDAs and precursors thereof from a cell population using novel surface markers.

Abstract: Disclosed herein are compositions, systems, and methods for modulating proliferation, differentiation and pluripotency of cells.

Abstract: The present disclosure relates generally to methods for treating, preventing, and/or ameliorating chronic kidney disease (CKD) and/or renal injury in a subject in need thereof. In particular, the methods disclosed herein comprise administering a therapeutically effective amount of a pharmaceutical composition comprising at least one Nlrp3 siRNA non-covalently conjugated to sidewall ammonium-functionalized carbon nanotubes (fCNTs), wherein the at least one Nlrp3 siRNA reduces the expression of NLR pyrin domain-containing protein 3 (NLRP3) in a subject diagnosed with, or at risk for CKD and/or renal injury.

Abstract: The instant disclosure provides antibodies that specifically bind to human PD-1 and antagonize PD-1 function. Also provided are pharmaceutical compositions comprising these antibodies, nucleic acids encoding these antibodies, expression vectors and host cells for making these antibodies, and methods of treating a subject using these antibodies.

Abstract: The present invention provides immunoresponsive cells, including T cells, cytotoxic T cells, regulatory T cells, and Natural Killer (NK) cells, expressing an antigen recognizing receptor and an inhibitory chimeric antigen receptor (iCAR). Methods of using the immunoresponsive cell include those for the treatment of neoplasia and other pathologies where an increase in an antigen-specific immune response is desired.

Abstract: Provided herein are compounds of Formula (I), and pharmaceutically acceptable salts or tautomers thereof. Also provided are pharmaceutical compositions, kits, and methods involving the inventive compounds for the treatment and/or prevention of an infectious disease (e.g., bacterial infection (e.g., Mycobacterium infection (e.g., tuberculosis)).

Abstract: The present technology relates to methods for treating, preventing, and/or ameliorating kinase mutation-associated neurodegenerative diseases, including BRAFV600E-associated neurodegenerative diseases, in a subject in need thereof. In particular aspects, the present technology relates to the use of BRAF, MEK, and/or CSF-IR inhibitors to treat, prevent, and/or ameliorate kinase mutation-associated neurodegenerative diseases, including BRAFV600E-associated neurodegenerative diseases.

Abstract: The present invention relates to methods and compositions for modulating the blood CSF barrier and for diagnosing, preventing and/or treating leptomeningeal metastasis. In particular embodiments of the invention, the permeability of the blood CSF barrier is modulated by agonists or antagonists of Complement Component 3 (C3) or its receptor.

Abstract: The present technology provides 13C- and 15N-labeled probes for imaging one or more mammalian cells using magnetic resonance. Thus, 13C- and 15N-labeled arginine (compound of formula I), xanthine (compounds of formula II and formula III), urea (compounds of formula IV), and glutamine (compounds of formula V), stereoisomers, tautomers, and pharmaceutically acceptable salts thereof are provided. Further methods of making the labelled probes and methods of using the probes to detect arginase, xanthine oxidase, and glutaminase metabolites and activity are provided.

Abstract: Molecular determinants of cancer response to immunotherapy are described, as are systems and tools for identifying and/or characterizing cancers likely to respond to immunotherapy.

Abstract: The present disclosure describes a compositions and methods for treatment of Hras-driven cancers. Administration of a farnesyltransferase inhibitor, for example, tipifarnib, alone or in combination with a MEK inhibitor can reduce tumor size and tumor growth in cancers such as poorly differentiated thyroid cancer (PDTC) and anaplastic thyroid cancer (ATC).

Abstract: The present disclosure provides antibodies that specifically bind to human OX40 receptor (OX40) and compositions comprising such antibodies. In a specific aspect, the antibodies specifically bind to human OX40 and modulate OX40 activity, e.g., enhance, activate, or induce OX40 activity, or reduce, deactivate, or inhibit OX40 activity. The present disclosure also provides methods for treating disorders, such as cancer, by administering an antibody that specifically binds to human OX40 and modulates OX40 activity, e.g., enhances, activates, or induces OX40 activity. Also provided are methods for treating autoimmune or inflammatory diseases or disorders, by administering an antibody that specifically binds to human OX40 and modulates OX40 activity, e.g., reduces, deactivates, or inhibits OX40 activity.

Abstract: Single chain peptides comprising either a cell penetrating HIV-TAT peptide sequence and a MYB:CBP complex interfering peptide sequence from MYB, or comprising a cell penetrating HIV-TAT peptide sequence, a CBP binding peptide sequence from CREB and a MYB:CBP complex interfering peptide sequence from MYB, are provided for use in preventing MYB:CBP complex formation and downstream events leading to cancer, in particular a leukemia. Both L-amino acid single chain peptides and retro-inverso single chain peptides are provided.

Abstract: The presently disclosed subject matter provides for in vitro methods of inducing differentiation of human stem cells into neural crest, cranial placode or non-neuro ectoderm precursors, and cells generated by such methods. The presently disclosed subject matter also provides for uses of such cells for treating neurodegenerative and pituitary disorders.

Abstract: The presently disclosed subject matter provides methods and compositions for enhancing immune responses toward tumor and pathogen antigens. It relates to fusion polypeptide that can be expressed in cells (e.g., immunoresponsive cells comprising an antigen-recognizing receptor) to improve the activity and/or efficiency of the cells. In certain embodiments, the fusion polypeptide comprises an extracellular domain and a transmembrane domain of a co-stimulatory ligand, and an intracellular domain of a co-stimulatory molecule.

Abstract: The presently disclosed subject matter provides polypeptide compositions comprising a chimeric antigen receptor (CAR) that targets mesothelin; and a dominant negative form of programmed death 1 (PD-1 DN). Also provided are immunoresponsive cells comprising such polypeptide compositions and uses of the polypeptide compositions and immunoresponsive cells for treatment, e.g., for treating solid tumors.

Abstract: The present invention relates to methods and compositions for modulating the blood CSF barrier and for diagnosing, preventing and/or treating leptomeningeal metastasis. In particular embodiments of the invention, the permeability of the blood CSF barrier is modulated by agonists or antagonists of Complement Component 3 (C3) or its receptor.