The data provided herewith show that, biomarkers found within the cells of a tumor or cancer may also be present at adequate levels within the patient's urine to enable detection. Method of diagnosis, patient selection and treatment are provided, along with kits and devices.

Provided are methods for the treatment of insulin resistance and insulin receptor diseases with SHP2 inhibitors, such as allosteric inhibitors of SHP2 and RNAi or siRNA that target SHP2 expression. Compositions and methods for delivery of SHP2 inhibitors, such as liver-targeting liposomes or nanoparticles, are also provided.

The present disclosure discloses use of a miRNA 148 cluster as a marker for diagnosing and/or treating cognitive impairment-associated diseases. The present disclosure provides use of the miRNA 148 cluster in the diagnosis and treatment of cognitive impairment-associated diseases. The expression level of the miRNA 148 cluster is detected using primers for the microRNA through cognitive impairment-associated disease models, and it is found that the expression of the miRNA 148 cluster is significantly reduced during the progression of the cognitive impairment-associated diseases. The miRNA 148 cluster is found to directly target p35 to inhibit hyperphosphorylation of Tau and can be negatively regulated by the upregulated PTEN in AD pathology. Upregulation of miRNA 148 cluster improves the cognitive dysfunction and inhibit the hyperphosphorylation of Tau in AD pathology, in which the PTEN/Akt/CREB and p35/CDK signaling pathways play a key role.

The present invention generally relates to methods of preparing leukocytes, particularly T cells, ex vivo for use in immunotherapy, particularly cancer immunotherapy. More specifically, the invention relates to methods for the preparation of leukocytes exhibiting cytotoxic properties for use in adoptive cell transfer. The invention also relates to cells and compositions including them for cancer immunotherapy. The invention also relates to methods of immunotherapy, particularly cancer immunotherapy. The present invention relates to a method for producing a leukocyte that has an enhanced capacity for killing a target cell, the method including contacting the leukocyte with a PTPN2 inhibitor in conditions for enabling the inhibitor to inactivate PTPN2 in the leukocyte, thereby producing a leukocyte that has an enhanced capacity for killing a target cell. Preferably, the leukocyte is contacted with the PTPN2 inhibitor in the absence of a T helper cell.

The invention in suitable embodiments is directed to dynamic bio-nanoparticle elements and bio-nanoparticle platforms employing such bio-nanoparticle elements. In one aspect, one or more elements of one or more types, formed from isolated, synthetic and or recombinant amino acid residues comprising in whole or in part one or more types of Clathrin and or Coatomer I/II proteins of one or more isoforms, execute one or more functions and or effect one or more ends, in vivo and or in vitro.

Provided herein are recombinant nucleic acids encoding chimeric priming receptors that bind ALPG/P, chimeric antigen receptors that bind MSLN, and shRNA that target FAS, PTPN2, and/or TOX. Also provided are systems of chimeric priming receptors that bind ALPG/P, chimeric antigen receptors that bind MSLN, and shRNA that target FAS, PTPN2, and/or TOX, cells expressing such proteins and shRNA, and methods of use thereof.

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).

A reversibly gated effector polypeptide e.g. a chimeric antigen receptor (protease-activating CD45-gate CAR) comprising an extracellular CD45 recruiting domain, a protease-cleavable linker, and a polypeptide comprising an extracellular ligand binding domain, a transmembrane domain, and an intracellular domain. Nucleic acids including vectors and expression vectors that encode the protease-activating CD45-gate CAR and cells including immune cells such as T cells that comprise and express the nucleic acids. Methods of treatment of various conditions including various forms of cancer comprising administering the cells including CAR T cell therapy. In some embodiments, the CD45 gate at least partially inhibits activation of the protease-activating CD45-gate CAR when the protease-activating CD45-gate CAR binds antigen. The inhibition is at least partially diminished, relieved and/or eliminated when the protease-activating CD45-gate CAR is exposed to a protease that can cleave the linker.

High affinity SIRP-α reagent are provided, which (i) comprise at least one amino acid change relative to the wild-type protein; and (ii) have an increased affinity for CD47 relative to the wild-type protein. Compositions and methods are provided for modulating phagocytosis in a mammal by administering a therapeutic dose of a pharmaceutical composition comprising a high affinity SIRPα reagent, which blocks the physiological binding interaction between SIRPα and its ligand CD47.

Provided herein are oligomeric compounds with conjugate groups targeting apolipoprotein C-III (ApoCIII). In certain embodiments, the ApoCIII targeting oligomeric compounds are conjugated to N-Acetylgalactosamine. Also disclosed herein are conjugated oligomeric compounds targeting ApoCIII for use in decreasing ApoCIII to treat, prevent, or ameliorate diseases, disorders or conditions related to ApoCIII. Certain diseases, disorders or conditions related to ApoCIII include inflammatory, cardiovascular and/or metabolic diseases, disorders or conditions. The conjugated oligomeric compounds disclosed herein can be used to treat such diseases, disorders or conditions in an individual in need thereof.