Abstract: The present invention provides a compound having the structure: or a pharmaceutically acceptable salt or ester thereof, and a method of treating a subject afflicted with pain, a depressive disorder, a mood disorder or an anxiety disorder by administering the compound to the subject.

Abstract: The invention provides compounds, methods, pharmaceutical compositions, and kits for the treatment of proliferative disorders such as cancer. In one aspect, the methods comprise compounds that inhibit the activity of protein kinases, such as cell division cycle (Cdc) kinase. In another aspect, the methods comprise compounds that inhibit Cdc7 and/or Dbf4 activity. In another aspect, the methods comprise compounds that exhibit anti-proliferative properties useful in treating diseases such as cancer. Compounds useful for any of the methods include compounds of the Formula (A) or (B): or pharmaceutically acceptable salts thereof. Exemplary compounds of Formula (A) or (B) include granaticin A, granaticin B, dihydrogranaticin A, dihydrogranaticin B, medermycin, and actinorhodin.

Abstract: This invention concerns various methods of using labeled HSP90 inhibitors to improve treatment of cancer patients with HSP90 inhibitors, including ex vivo and in vivo methods for determining whether a tumor will likely respond to therapy with an HSP90 inhibitor.

Abstract: The present disclosure provides novel dominant negative Fas polypeptides comprising a first modification in the cytoplasmic domain and a second modification in the N-terminal region of human Fas. The present disclosure also provides cells comprising such novel dominant negative Fas polypeptides and an antigen-recognizing receptor (e.g., a chimeric antigen receptor (CAR) or a T cell receptor (TCR)). Also provided are uses of the cells for treatment, e.g., for treating tumors and pathogen infections.

Abstract: The present disclosure provides methods and compositions for enhancing the immune response toward cancers and pathogens. The presently disclosed subject matter provides methods and compositions for enhancing the immune response toward cancers and pathogens. It relates to cells comprising a c-Kit mutant, e.g., a c-Kit mutant comprising an activating mutation. The cells can further comprise an antigen-recognizing receptor (e.g., a chimeric antigen receptors (CAR) or a T cell receptors (TCR)). The presently disclosed subject matter relates to the use of cells for treatment, e.g., treating cancers.

Abstract: The present invention provides soluble single wall nanotube (SWNT) constructs functionalized with a plurality of a targeting moiety and a plurality of one or more payload molecules attached thereto. The targeting moiety and the payload molecules may be attached to the soluble SWNT via a DNA or other oligomer platform attached to the SWNT. These soluble SWNT constructs may comprise a radionuclide or contrast agent and as such are effective as diagnostic and therapeutic agents. Methods provided herein are to diagnosing or locating a cancer, treating a cancer, eliciting an immune response against a cancer or delivering an anticancer drug in situ via an enzymatic nanofactory using the soluble SWNT constructs.

Abstract: The presently disclosed subject matter provides for chimeric receptors that target ADGRE2 and chimeric receptors that target CLEC12A. The presently disclosed subject matter also provides for cells comprising the ADGRE2-targeted chimeric receptors, cells comprising the CLEC12A-targeted chimeric receptors, and cells comprising the ADGRE2-targeted chimeric receptors and the CLEC12A-targeted chimeric receptors. The presently disclosed subject matter further provides uses of such cells for treating tumors, e.g., AML.

Abstract: The present invention relates to triterpene glycoside saponin-derived adjuvants, syntheses thereof, intermediates thereto, and uses thereof. QS-7 is a potent immuno-adjuvant that is significantly less toxic than QS-21, a related saponin that is currently the favored adjuvant in anticancer and antiviral vaccines. Tedious isolation and purification protocols have hindered the clinical development of QS-7. A novel semi-synthetic method is provided wherein a hydrolyzed prosapogenin mixture is used to synthesize QS-7, QS-21, and related analogs, greatly facilitating access to QS-7 and QS-21 analogs for preclinical and clinical evaluation.

Abstract: The present invention provides a fluorescent silica-based nanoparticle that allows for precise detection, characterization, monitoring and treatment of a disease such as cancer. The nanoparticle has a range of diameters including between about 0.1 nm and about 100 nm, between about 0.5 nm and about 50 nm, between about 1 nm and about 25 nm, between about 1 nm and about 15 nm, or between about 1 nm and about 8 nm. The nanoparticle has a fluorescent compound positioned within the nanoparticle, and has greater brightness and fluorescent quantum yield than the free fluorescent compound. The nanoparticle also exhibits high biostability and biocompatibility. To facilitate efficient urinary excretion of the nanoparticle, it may be coated with an organic polymer, such as poly(ethylene glycol) (PEG). The small size of the nanoparticle, the silica base and the organic polymer coating minimizes the toxicity of the nanoparticle when administered in vivo.

Abstract: The presently disclosed subject matter provides cells and compositions for improved immunotherapy and methods of using such cells and compositions. It relates to cells comprising a ligand-recognizing receptor (e.g., an antigen-recognizing receptor, e.g., a chimeric antigen receptor (CAR) or a T-cell Receptor (TCR)) and an IgG-degrading enzyme or a fragment thereof. The IgG-degrading enzyme rapidly cleaves IgG. The IgG-degrading enzyme serves as a biomolecular shield against the host humoral response. The cells have increased resistance to host humoral response (e.g., an antibody-driven host humoral response), which allows for prolonged persistence of the cells, leading to enhanced activity of the cells.

Abstract: The presently disclosed subject matter provides for antigen-recognizing receptors that specifically target CD371 and cells comprising such CD371-targeted antigen-recognizing receptors. The presently disclosed subject matter further provides uses of the CD371-targeted antigen-recognizing receptors for treatment.

Abstract: The presently disclosed subject matter provides antibodies or antigen-binding fragments thereof that bind to CD371 and methods of using such antibodies or antigen-binding fragments thereof same.

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 present invention provides a compound having the structure: or a pharmaceutically acceptable salt or ester thereof, and methods of using the compound to treat pain, depressive disorders, mood disorders, anxiety disorders, opioid use disorder, and opioid withdrawal symptoms.

Abstract: We have discovered that administering anti-ceramide antibody treats and prevents an array of diseases mediated by cytolytic T lymphocyte (CTLs)-induced killing and by damage to endothelial microvasculture, including radiation-induced GI syndrome, Graft vs. Host diseases, inflammatory diseases and autoimmune diseases. We have also discovered new anti-ceramide monoclonal antibodies, that have therapeutic use preferably in humanized form to treat or prevent these diseases.

Abstract: The present invention is directed to methods of diagnosing, prognosing, and monitoring cancer in a subject. These methods involves selecting a subject having cancer, and obtaining, from the selected subject, a sample containing exosomal DNA. The presence or absence of one or more mutations in BRAF and/or EGFR is detected in the exosomal DNA sample from the subject, and a diagnosis and/or prognosis of the cancer is given based on the detection of the one or more mutations in BRAF and/or EGFR. The present invention further relates to methods of treating a subject having cancer and/or monitoring a subject response to therapy based on the detection of one or more mutations in BRAF and/or EGFR in the exosomal DNA sample.

Abstract: The development of a new, targeted drug delivery paradigm coupled to improved PI3K inhibitors (e.g., PI3K? inhibitors) represents a significant advance in cancer therapy. Provided herein are compounds, such as compounds of Formula (I) and (II), and pharmaceutically acceptable salts, hydrates, solvates, polymorphs, co-crystals, tautomers, stereoisomers, isotopically labeled derivatives, and prodrugs thereof. The compounds provided herein are PI3K (e.g., PI3K?) inhibitors and are therefore useful for the treatment and/or prevention of various diseases (e.g., proliferative diseases such as cancer). Also provided herein are nanoparticles and nanogels (e.g., P-selectin targeting nanoparticles) comprising PI3K inhibitors, such a compound described herein. In certain embodiments, a nanoparticle or nanogel described herein encapsulates a compound described herein for targeting delivery to cancer cells or tumors.

Abstract: Provided herein are single wall nanotube constructs to which are convalently linked a plurality of a bifunctional chelator, a therapeutic or a diagnostic radionuclide chelated to each bifunctional chelator and a plurality of morpholino oligonucleotides conjugated to the single wall nanotube. Also provided are single wall nanotube complexes which have the morpholino oligonucleotides on the single wall nanotube constructs hybridized to other morpholino oligonucleotides. The other morpholino oligonucleotides are each conjugated to a therapeutic antibody.

Abstract: The invention provides compounds, methods, pharmaceutical compositions, and kits for the treatment of proliferative disorders such as cancer. In one aspect, the methods comprise compounds that inhibit the activity of protein kinases, such as cell division cycle (Cdc) kinase. In another aspect, the methods comprise compounds that inhibit Cdc7 and/or Dbf4 activity. In another aspect, the methods comprise compounds that exhibit anti-proliferative properties useful in treating diseases such as cancer. Compounds useful for any of the methods include compounds of the Formula (A) or (B): or pharmaceutically acceptable salts thereof. Exemplary compounds of Formula (A) or (B) include granaticin A, granaticin B, dihydrogranaticin A, dihydrogranaticin B, medermycin, and actinorhodin.

Abstract: The present invention provides a compound having the structure: or a pharmaceutically acceptable salt or ester thereof, and a method of treating a subject afflicted with pain, a depressive disorder, a mood disorder or an anxiety disorder by administering the compound to the subject.