The present invention describes the cloning and molecular and cellular characterization of a novel protein with homology to the IL-17 receptor. The gene was cloned by virtue of its proximity to a common site of retroviral integration in a murine acute myeloid leukemia. The gene described herein possibly codes for a novel interleukin receptor that binds an as yet unidentified cytokine ligand, and may be useful in cancer diagnostics and therapies that rely on immune system modulation.

P-Selectin on platelets and endothelium binds cell surface chondroitin sulfate (CS) proteoglycans, which are abundantly and stably expressed on the surface many cancer cells. Binding of the cancer cells through the CS moieties may be blocked to inhibit the interaction of cancer cells with platelets and endothelium. The present inventors disclose compositions and methods for the inhibition of cancer metastasis.

Novel alkylindoles that bind tightly to cannabinoid receptors and are neutral antagonists for the cannabinoid 1 receptor and agonists for the cannabinoid 2 receptor are provided. These compounds are useful for treating alcoholism and drug abuse and for treating obesity.

Provided herein are compounds, comprising Formula (I) or Formula (II), and their pharmaceutically acceptable salts. Also provided are pharmaceutical compositions comprising a pharmaceutically acceptable excipient and at least one compound of Formula (I) and (II), singly or in combination with other pharmaceutically active ingredients, such as anti-inflammatory agents or anticancer agents.

The present invention used gene expression profiling in large uniformly treated population of patients with myeloma to identify genes associated with poor prognosis. It also demonstrated that over-expression of CKS1B gene, mainly due to gene amplification that was determined by Fluorescent in-situ hybridization to impart a poor prognosis in multiple myleoma.

The present disclosure provides derivatives of melampomagnolide B (MMB), including carbonates, carbamates, and thiocarbamates. The derivatives may be synthesized via an MMB triazole intermediate. These derivatives are useful for treating cancer in humans.

A method is presented for treating an inflammatory skin disorder in a human comprising: topically applying to the skin a composition comprising alpha-melanocyte stimulating hormone (αMSH) or an αMSH analog in an amount effective to reduce skin inflammation in the human.

A device and method of using the device to detect the presence and composition of clots and other target objects in a circulatory vessel of a living subject is described. In particular, devices and methods of detecting the presence and composition of clots and other target objects in a circulatory vessel of a living subject using in vivo photoacoustic flow cytometry techniques is described.

Recombinant T cell clonotypes are provided that express T cell receptor alpha and T cell receptor beta polypeptides with specificity for human papillomavirus (HPV) type 16 E6 protein and that amplify in response to a therapeutic vaccine and traffic to ovarian lesional tissue in a patient whose HPV lesions regressed in response to the vaccine. Recombinant T cells expressing appropriate TCR alpha and beta complimentarity determining sequences for HPV 16 E6 binding and treating HPV-cased cancers are provided. Bifunctional proteins having TCR alpha and beta segments that bind to HPV 16 E6 residues 91-115 and a single chain Fv anti-CD3 antibody domain are provided. These bifunctional proteins can direct T cells to HPV-infected cells.

The present disclosure provides compositions and methods for selectively killing senescent cells, wherein the selective killing of senescent cells delays aging and treats age-related disorders.

“The present disclosure provides methods of inhibiting PARG in cancer cells, including methods comprising administering a PARG inhibitor that modulates position Tyr795 in PARG. Also provided herein are methods of treating and/or preventing cancer comprising administering a PARG inhibitor. In some embodiments, the PARG inhibitors are of the formula: wherein the variables are defined herein.

This invention describes a small molecule proteolysis targeting chimera (PROTAC) strategy to degrade the NEK2 (Never in Mitosis Related Kinase 2) protein and methods of use thereof. The NEK2 PROTAC consists of three, key regions: a NEK2 ligand to bind the NEK2 protein, a linker region to link the NEK2 ligand to a ligase ligand, and the ligase ligand.

The present invention provides methods of treating bone loss or cancer using CST6. In these methods, CST6 may be provided as a recombinant CST6 protein, a polynucleotide construct comprising CST6, or an immune cell expressing CST6 protein.

Disclosed herein are RNA methyltransf erase inhibitors and methods of using and making the same. The inhibitors may be used in a method for the treatment of a subject in need of a treatment for a cancer by administering an effective amount of the RNA methyltransferase inhibitor and an effective amount of a DNA damaging agent to the subject.

The present invention provides dehydroleucodine derivatives. In particular, the present invention provides amine derivatives of dehydroleucodine and methods of using dehydroleucodine and the amine derivatives of dehydroleucodine to inhibit the growth of cancer cells.

Mutant Myxoma viruses are provided herein and methods of using these viruses to treat cancer or elicit an interferon response in a subject are also provided. The mutant Myxoma virus is modified to reduce or eliminate the activity or expression of Myxoma virus protein M62 as compared to a control virus. The mutant virus is capable of stimulating an interferon response in subjects after administration and can also lead to inhibition, reduction or elimination of the CD14+ tumor associated macrophage inhibition of CD4+ T cells in a subject having cancer and lead to a change in the tumor microenvironment to treat the cancer or work in combination with other cancer therapeutics to treat the cancer as described herein.

The present disclosure provides compositions and methods for selectively killing cancer cells, wherein the composition comprises a compound of Formula (I). The selective killing of cancer cells occurs with an improved potency and safety profile compared to similar compounds. In particular, the compositions and methods of the invention show reduced platelet toxicity and retained or improved toxicity in cancer cells.

The present disclosure provides SL and SL derivatives comprising a polar substituent adjacent to the lactone ring. Additionally, the present disclosure provides methods of using the SL and SL derivatives to inhibit the growth of leukemic cancer cells.

The present inventors have developed antigen-binding reagents and antigen-binding conjugates that recognize a cancer-specific glycan (carbohydrate) modification on the human Periostin protein. Various in vitro and in vivo diagnostic and/or therapeutic methods using these compositions are also disclosed herein specifically for treating cancers that have amplification of the Mgat3 gene.

The present disclosure provides compositions and methods for selectively killing senescent cells, wherein the composition comprises piperlongumine (PL) or derivative thereof. The selective killing of senescent cells may delay aging and/or treat age-related disorders.

Gene expression profiling is a powerful tool that has varied utility. It enables classification of multiple myeloma into subtypes and identifying genes directly involved in disease pathogenesis and clinical manifestation. The present invention used gene expression profiling in large uniformly treated population of patients with myeloma to identify genes associated with poor prognosis. It also demonstrated that over-expression of CKS1B gene, mainly due to gene amplification that was determined by Fluorescent in-situ hybridization to impart a poor prognosis in multiple myeloma. It is further contemplated that therapeutic strategies that directly target CKS1B or related pathways may represent novel, and more specific means of treating high risk myeloma and may prevent its secondary evolution.

A method is presented for treating herpes simplex virus (HSV) infection comprising: (a) locally administering a substance that induces a delayed type hypersensitivity (DTH) response to a patient at a site of an HSV lesion to induce a DTH response at the site of the lesion during one or more outbreaks of the HSV infection.

Devices and methods for peripheral nerve stimulation with an electrode assembly having a lead body with a tapered transition, at least one anchor, and at least one distal lead configured to connect to the lead body are disclosed.

The disclosure provides a method of preventing or reducing protein aggregates using combretastatin-A4 (CA4) or an analog thereof. The disclosure also provides methods of reducing the risk, delaying the onset, delaying or slowing the progression, or reversing the signs or symptoms of a neurodegenerative (or other age-progressive) disease using a combretastatin-A4 (CA4) or an analog thereof. The combretastatin-A4 (CA4) or an analog thereof may bind glial fibrillary acidic protein (GFAP). The combretastatin-A4 (CA4) or an analog thereof is described by compounds of Formula (I).

The invention involves the discovery that if dendritic cells loaded with a tumor antigen are cultured in interleukin-15 (IL-15), or if T cells activated by the dendritic cells are cultured in IL-15, Treg activity that is specific for the tumor antigen is reduced. This reduction in Treg activity results in an increase in anti-tumor immune response. Another embodiment of the invention involves the discovery that incubating dendritic cells with a MAP kinase inhibitor in combination with IL-15 gives synergistic benefits when the dendritic cells are used to activate T cells. Dendritic cell and T cell compositions incubated with IL-15 or a MAP kinase inhibitor are provided.

Compositions useful to induce anti-TACA immune response and kits comprising the same and methods of using the compositions to treat and prevent cancer are disclosed. Isolated human antibodies which bind to a carbohydrate mimetic peptide and methods of making the same and using the same to treat and prevent cancer are disclosed. Isolated human NK cells useful to kill tumor cells, and isolated human dendritic cells, and methods of making the same and using the same to treat and prevent cancer are disclosed.

The present invention relates novel heterocyclic analogs of combretastatin, their synthesis, and their use as anti-cancer compounds. In particular, compounds of Formula (I), Formula (II), and Formula (V) are provided.

The present disclosure provides dimers of melampomagnolide B (MMB), including carbamate, carbonate, succinic amide, ester and carboxamide dimers of MMB. These derivatives are useful for treating cancer in humans, in particular in treating leukemia, including acute myelogenous leukemia (AML).

The invention generally features compositions and methods for expanding long term hematopoietic stem cells (HSCs) in a population of cells. In particular, the invention relates to a method of expanding long term HSCs by culturing an initial population of HSCs with macrophages that promote self-renewal of long term HSCs. The expanded cell population provides a source of cells for therapeutic treatments utilizing HSC transplantation.