39 results about "TRAIL Receptors" patented technology

The present invention provides Tenascin-3 FnIII domain-based multimeric scaffolds that specifically bind to TRAIL Receptor 2 (TRAIL R2), a cell membrane receptor involved in apoptosis. The invention further provides engineered variants with increased affinity for the target, increased stability, and reduced immunogenicity. Furthermore, the present invention is related to engineered multivalent scaffolds as prophylactic, diagnostic, or therapeutic agents, and their uses against diseases caused by cells expressing TRAIL R2, in particular to a therapeutic use against cancer.

In accordance with the present invention, there are provided isolated mammalian TRAIL receptor proteins, antibodies thereto, therapeutic compositions, and nucleic acids encoding such. Bioassays and therapeutic methods employing invention DR5 and TRAIL-R3 proteins are also provided.

In accordance with the present invention, there are provided isolated mammalian TRAIL receptor proteins, antibodies thereto, therapeutic compositions, and nucleic acids encoding such. Bioassays and therapeutic methods employing invention DR5 and TRAIL-R3 proteins are also provided.

The present invention relates to a novel human gene encoding a polypeptide which is a member of the TNF receptor family, and has now been found to bind TRAIL. More specifically, an isolated nucleic acid molecule is provided encoding a human polypeptide named tumor necrosis factor receptor-5, sometimes referred to as "TNFR-5" or "TR5," and now referred to hereinafter as "TRAIL receptor without intracellular domain" or "TRID." TRID polypeptides are also provided, as are vectors, host cells, and recombinant methods for producing the same. The invention further relates to screening methods for identifying agonists or antagonists of TRAIL polypeptide activity. Also provided are diagnostic and therapeutic methods utilizing such compositions.

Provided are fusion proteins comprising a first domain and a second domain, wherein the first domain comprises a polypeptide that binds to and triggers PD-1 and the second domain comprises a polypeptide that binds to and triggers a TRAIL receptor or Fas. In some embodiments, the polypeptide that binds to and triggers PD-1 comprises at least a portion of the extracellular domain of PD-L1 or PD-L2 and the second domain comprises at least a portion of the extracellular domain of TRAIL or Fas ligand. Also provided are methods for treating autoimmune, alloimmune or inflammatory diseases, and methods for treating cancer, using the fusion proteins.

Provided herein are specific TRAIL receptor agonist proteins, nucleic acids encoding the same, and methods of treating a subject having a TRAIL-associated disease or disorder. The TRAIL receptor agonist proteins provided herein comprise three soluble TRAIL domains and an Fc fragment. The TRAIL receptor agonist proteins are substantially non-aggregating and suitable for therapeutic, diagnostic and / or research applications.

The invention relates to methods of treating HIV by administering a TRAIL receptor activator. The invention also relates to methods for inducing apoptosis in an HIV reservoir cell by contacting the cell with TRAIL receptor activator such as an M-CSF effector kinase inhibitor.

In accordance with the present invention, there are provided isolated mammalian TRAIL receptor proteins, antibodies thereto, therapeutic compositions, and nucleic acids encoding such. Bioassays and therapeutic methods employing invention DR5 and TRAIL-R3 proteins are also provided.

This invention relates generally to the preparation of TRAIL receptor-binding agents and uses of the same. In particular, the present invention relates to the preparation of anti-TRAIL receptor antibodies which recognize a common antigen determinant (i.e., epitope) shared by TRAIL-R1 and TRAIL-R2 receptors and their use for TRAIL receptor detection and modulation of TRAIL receptor-mediated function. The TRAIL receptor-binding agents are useful to induce apoptosis in human cancer cells. These targets may either express one or both TRAIL-R1 or TRAIL-R2. The invention provides for the use of the TRAIL receptor-binding agents of the invention in cancer therapy.

Methods and composition are provided for modulating innate immunity by modulating activation of the TRAIL receptor. Signaling through the TRAIL-R inhibits the responsiveness of cells including dendritic cells, macrophages, and the like. The activity of these cells is increased or decreased by the administration of agents that inhibit or activate TRAIL-R signaling. Innate immunity includes the production of cytokines that act on the immune system.

The present invention discloses a monoclonal antibody against the extracellular domain of human tumor necrosis factor-related apoptosis-inducing ligand receptor DR5 (death receptor 5), The present invention also provides a method of producing the monoclonal antibody, amino acid sequences of the variable regions of the monoclonal antibody's heavy chain and light chain, as well as use of the monoclonal antibody for preparation of a medicament in the treatment of various cancers and / or AIDS.

Pro-apoptotic agents such as ligands and agonists of agonistic TRAIL receptors can induce or increase apoptosis of cells that cause fibrosis and underlying diseases such as liver, pancreatic, lung and skin diseases characterized by fibrosis, cirrhosis, or complications thereof. The compositions and methods can be used to selectively remove activated hepatic stellate cells (HSCs), the originators of liver fibrosis and cirrhosis, and activated pancreatic stellate cells (PSCs), the originators of pancreas fibrosis and pancreatitis, and can be effective to reduce or prevent further chronic fibrosis by simultaneously reducing multiple fibrosis-associated molecules secreted or induced by such activated stellate cells. The compositions are typically effective to target agonistic TRAIL receptors such as TRAIL-R1 / DR4 and TRAIL-R2 / DR5 that are selectively expressed in activated HSCs and PSCs in physiological conditions. Ligands and agonists that can be used to target agonistic TRAIL receptors include, but are not limited to, TRAIL-R1 / DR4 and / or TRAIL-R2 / DR5 agonists.

Pro-apoptotic agents such as ligands and agonists of agonistic TRAIL receptors can induce or increase apoptosis of cells that cause fibrosis and underlying diseases such as liver, pancreatic, lung and skin diseases characterized by fibrosis, cirrhosis, or complications thereof. The compositions and methods can be used to selectively remove activated hepatic stellate cells (HSCs), the originators of liver fibrosis and cirrhosis, and activated pancreatic stellate cells (PSCs), the originators of pancreas fibrosis and pancreatitis, and can be effective to reduce or prevent further chronic fibrosis by simultaneously reducing multiple fibrosis-associated molecules secreted or induced by such activated stellate cells. The compositions are typically effective to target agonistic TRAIL receptors such as TRAIL-R1 / DR4 and TRAIL-R2 / DR5 that are selectively expressed in activated HSCs and PSCs in physiological conditions. Ligands and agonists that can be used to target agonistic TRAIL receptors include, but are not limited to, TRAIL-R1 / DR4 and / or TRAIL-R2 / DR5 agonists.

Methods and composition are provided for modulating innate immunity by modulating activation of the TRAIL receptor. Signaling through the TRAIL-R inhibits the responsiveness of cells including dendritic cells, macrophages, and the like. The activity of these cells is increased or decreased by the administration of agents that inhibit or activate TRAIL-R signaling. Innate immunity includes the production of cytokines that act on the immune system.

A specific antibody combined TRAIL acceptor 1(TRAIL-R1) and / or TRAIL acceptor 2(TRAIL-R2), its amino-acid sequence and nucleotide sequence for encoding it and its usage in treatment of tumor are disclosed.

The invention discloses a screening system of anti-tumor drugs based on a TRAIL receptor signal channel. The screening system comprises fusion gene cells (A549-pDR5-luc and H157-pDR5-luc), CCLR and luciferase detection substrate, wherein the fusion gene cells comprise a DR5 promoter and a luciferase reporter gene. According to the invention, through determining the rise of luciferase reporter gene expression in the A549-pDR5-luc and H157-pDR5-luc cells on which a compound to be screened acts to screen a compound improving the expression of DR5, the screening of anti-tumor drugs is realized. The screening system has characteristics of short experimental period, quick detection process, high sensitivity and wide application, and provides a new method for the screening of high through-put anti-tumor drugs.

The present invention discloses the preparation process of biosensitive TRAIL antibody membrane. The preparation process includes the following steps: A. semiconductor manufacture process of making MOSFET including source, drain, and grid of non-metal insulating material SiN with P-type silicon material; B. silanizing sensitive SiN grid; C. fixing protein A onto the surface of SiN via adsorption, drying at room temperature, closing with ox serum protein, cleaning with buffering phosphate solution and drying to form composite SiN-protein A sensitive membrane; and D. fixing antibody to TRAIL receptor via adsorption onto protein A, drying at room temperature, cleaning with buffering phosphate solution and drying to form the superposed biosensitive SiN-protein A- TRAIL receptor antibody membrane. The present invention also relates to multipath TRAIL receptor detection system with the membrane and method of detecting four TRAIL receptors of tumor cell apoptosis factor.

Pro-apoptotic agents such as ligands and agonists of agonistic TRAIL receptors can induce or increase apoptosis of cells that cause fibrosis and underlying diseases such as liver, pancreatic, lung and skin diseases characterized by fibrosis, cirrhosis, or complications thereof. The compositions and methods can be used to selectively remove activated hepatic stellate cells (HSCs), the originators of liver fibrosis and cirrhosis, and activated pancreatic stellate cells (PSCs), the originators of pancreas fibrosis and pancreatitis, and can be effective to reduce or prevent further chronic fibrosis by simultaneously reducing multiple fibrosis-associated molecules secreted or induced by such activated stellate cells. The compositions are typically effective to target agonistic TRAIL receptors such as TRAIL-R1 / DR4 and TRAIL-R2 / DR5 that are selectively expressed in activated HSCs and PSCs in physiological conditions. Ligands and agonists that can be used to target agonistic TRAIL receptors include, but are not limited to, TRAIL-R1 / DR4 and / or TRAIL-R2 / DR5 agonists.

Provided herein are specific TRAIL receptor agonist proteins, nucleic acids encoding the same, and methods of treating a subject having a TRAIL-associated disease or disorder. The TRAIL receptor agonist proteins provided herein comprise three soluble TRAIL domains and an Fc fragment. The TRAIL receptor agonist proteins are substantially non-aggregating and suitable for therapeutic, diagnostic and / or research applications.

Provided is a fusion protein comprising a polypeptide component that blocks binding of CD47 to SIRP alpha and a polypeptide that binds to and triggers a TRAIL receptor or Fas. Also provided is a method of treating cancer in a patient comprising administering the fusion protein of the invention to a patient in need of such treatment.

TRAIL receptor-binding agents exert therapeutic effects on tumor inhibition in vitro and in vivo, alone or in combination with an anti-cancer biologic. In particular, methods for the treatment of cancer comprise administering a TRAIL receptor binding agent, alone or in combination with TRAIL and / or interferon alpha-2b.

Described herein is TRAIL receptor targeting therapy in combination with metformin for treatment of cancer in humans. Using TRAIL receptor targeting therapy such as the TRAIL molecule, agonistic human monoclonal antibodies against TRAIL receptors, or peptides targeting TRAIL receptors in combination with metformin for the treatment of all types of cancer allows to obtain an optimum therapeutical effect at any time of the progression of the disease.

Therapeutic compositions comprising at least one 8-substituted-dibenzylbutyrolactone lignan, preferably a lignan is selected from the group of nortrachelogenin, diasteromeric forms of nortrachelogenin, isomeric forms of nortrachelogenin and combinations thereof as well as 8-methylmatairesinol and 8-methyldimethylmatairesinol, for use in a method of treating cancer or a similar condition wherein the growth factor signaling pathway of a mammal is deregulated. The invention also provides therapeutic pharmaceutical combinations comprising a hydroxy-dibenzylbutyrolactone lignan and at least one TRAIL receptor agonist. The hydroxy-dibenzylbutyrolactone lignans and a TRAIL receptor agonist can be used as a combined preparation for administration to a patient simultaneously, separately or spaced out over a period of time in treating cancer.

The present invention discloses TRAIL receptor-binding agents, and their therapeutic effects on tumor inhibition in vitro and in vivo, alone or in combination with various chemotherapeutic agents. In particular, the present invention discloses methods for the treatment of cancer, comprising administrating a TRAIL receptor binding agent of the present technology, alone or in combination with a chemotherapeutic agent.

The present invention provides Tenascin-3 FnIII domain-based multimeric scaffolds that specifically bind to TRAIL Receptor 2 (TRAIL R2), a cell membrane receptor involved in apoptosis. The invention further provides engineered variants with increased affinity for the target, increased stability, and reduced immunogenicity. Furthermore, the present invention is related to engineered multivalent scaffolds as prophylactic, diagnostic, or therapeutic agents, and their uses against diseases caused by cells expressing TRAIL R2, in particular to a therapeutic use against cancer.

Methods of treating an autoimmune disease such as rheumatoid arthritis, methods of increasing apoptosis of pro-inflammatory immune cells or synoviocytes, methods of increasing the quantity of the anti-inflammatory regulatory T cells, and methods of slowing the progression of inflammation in a subject include systemically administering to the subject a pharmaceutical composition including an effective amount of a TRAIL-conjugate. Preferably, the TRAIL-conjugate is effective for at least 3 days, more preferably at least 7 days, without being part of a nanocomplex that modulates the circulation half-life or release kinetics of the TRAIL-conjugate. Combination therapies including administering a second active agent, most preferably a TNF-α inhibitor, as well as pharmaceutical composition dosage units including a TRAIL-conjugate and a TNF-α inhibitor in an effective amount for a single once weekly dose for treatment of rheumatoid arthritis are also provided.

The present invention relates to methods and materials for treating an individual with KRAS-mutated cancer or a cancer in which ROCK is inhibited independently of mutated KRAS. The invention is based on the prevention or disruption of the binding of TRAIL-Receptor to its ligand, TRAIL, in vivo, for example by use of an agent that neutralises TRAIL and / or a the TRAIL-Receptor (such TRAIL-R2) and / or diminishes TRAIL / TRAIL-Receptor activity, thereby reducing cancer cell transformation, migration and metastasis, prolonging survival of patients.

Provided are fusion proteins comprising a first domain and a second domain, wherein the first domain comprises a polypeptide that binds to and triggers PD-1 and the second domain comprises a polypeptide that binds to and triggers a TRAIL receptor or Fas. In some embodiments, the polypeptide that binds to and triggers PD-1 comprises at least a portion of the extracellular domain of PD-L1 or PD-L2 and the second domain comprises at least a portion of the extracellular domain of TRAIL or Fas ligand. Also provided are methods for treating autoimmune, alloimmune or inflammatory diseases, and methods for treating cancer, using the fusion proteins.