118results about "Tumor necrosis factor" patented technology

The invention relates generally to compositions and methods for purifying the desired species from a mixture of desired heterodimer and contaminating homodimer immunoglobulin variants by modifying the isoelectric point(s) of the individual chains.

The present invention relates to multispecific antigen binding proteins that comprise an antigen-binding regions specific for a tumor-associated antigen (TAA), an antigen-binding region that specifically binds an epitope of a γδ T cell receptor (TCR), a γδ T cell-activating cytokine, and optionally, a γδ T cell co-stimulatory agonist. The γδ T cell-activating cytokine preferably is at least 5 one of an interleukin 21 receptor (IL21R) agonist and an interleukin 15 receptor (IL15R) agonist. The γδ T cell co-stimulatory agonist cytokine preferably is at least one of a 4-1BB agonist, a CD27 agonist and a GITR agonist. The multispecific antigen binding proteins of the invention specifically redirect and activate γδ T cell to lyse targeted tumor cells. The invention further relates to the use of such multispecific antigen binding proteins in the treatment of cancer, preferably a cancer 10 expressing the TAA.

Provided herein are macromolecules that conditionally induce a cellular effector function (e.g., a biological or therapeutic activity) based on the presence of a disease signature ligand, compositions comprising the same, and methods of using the same.

The application relates to the technical field of biological medicine, in particular to a medicine for combined treatment of tumors by using a recombinant oncolytic virus and a small-molecule anticancer drug. The method comprises the following steps: combined treatment of tumors by using a recombinant oncolytic virus and a small-molecule anticancer drug; the small-molecule anticancer drug is a small-molecule anticancer drug targeting Parp; the recombinant oncolytic virus comprises M protein, G protein, N protein, P protein and L protein after site-directed mutagenesis. The application can kill tumor cells by using a recombinant oncolytic virus and a small-molecule anticancer drug, and the curative effect is 1+1>2.

Provided herein are novel constructs comprising gold nanoparticles bound to two types of cytokines, wherein the two types of cytokines comprise Tumor Necrosis Factor alpha (TNF ) and a cytokine selected from the group consisting of Interferon gamma (IFN ) and lnterleukin-12. Further provided is a method for treating cancer in a subject in need thereof.

Described herein are methods, systems, compositions, and kits useful for the diagnosis and / or treatment of a disease or condition in a subject. The present disclosure relates to methods and systems for identifying and stratifying patients suitable for treatment with a modulator of RNASET2, as described herein.

This application relates to the biomedical technology field, and more specifically to a tumor therapy method combining recombinant oncolytic viruses and small molecule anticancer drugs. Specifically, it includes the step of treating a tumor using recombinant oncolytic viruses and small molecule anticancer drugs in combination, wherein the small molecule anticancer drugs include ALK-targeting small molecule anticancer drugs, BTK-targeting small molecule anticancer drugs, EGFR-targeting small molecule anticancer drugs, FGFR-targeting small molecule anticancer drugs, HER2-targeting small molecule anticancer drugs, Parp-targeting small molecule anticancer drugs, PI3K-targeting small molecule anticancer drugs, VEGFR-targeting small molecule anticancer drugs, CDK4 / 6-targeting small molecule anticancer drugs, and KRAS-targeting small molecule anticancer drugs, and the recombinant oncolytic viruses include site-directed mutagenesis of M protein, G protein, N protein, P protein, and L protein. In this application, it is possible to achieve an effect greater than 1+1 by using recombinant oncolytic viruses and low-molecular-weight anticancer drugs in combination to attack and kill tumor cells.

The present invention relates to bi-, tri-, or oligospecific anti-TNFR1 fusion proteins, which are monovalent for TNFR1 and exhibit excellent productivity and strong conditional TNFR1 agonism. The invention also relates to bi-, tri-, or oligospecific anti-TNFR1 nanobody fusion proteins which display strong conditional TNFR1 agonism upon binding to cell surface or extracellular matrix antigens such as PD-L1 or CD70. The invention also relates to methods of producing such bi-, tri-, or oligospecific anti-TNFR1 nanobody fusion protein constructs, pharmaceutical compositions comprising the same, as well as their uses for treating cancer.

The present disclosure provides immunomodulatory fusion proteins-metal hydroxide complexes comprising an immunomodulatory domain adsorbed to a metal hydroxide via ligand exchange. The disclosure also features compositions and methods of using the same, for example, to treat cancer.

Provided are D-peptide binding agents of TNF [alpha], multimers thereof, and methods of using D-peptides and multimers thereof.

The present invention relates to modified myeloid cells or iPS or HSCs comprising a chimeric antigen receptor (CAR), or modified induced pluripotent stem cells (iPS) or hematopoietic stem cells (HSCs) comprising a CAR, the CAR comprising an extracellular antigen binding domain that binds to a tumor antigen or a tumor microenvironment (TME) antigen, a transmembrane domain, and a first intracellular signaling domain comprising the cytoplasmic tail of CD40 fused to a second intracellular signaling domain comprising the intracellular domain of CD3ζ. The present invention also relates to therapeutic uses thereof.

The present invention relates to modified myeloid cells comprising a chimeric antigen receptor (CAR), or modified induced pluripotent stem cells (iPS) or hematopoietic stem cells (HSC) comprising a CAR, the CAR comprising an extracellular antigen-binding domain that binds to a tumor antigen or a tumor microenvironment (TME) antigen; a transmembrane domain; and an intracellular signaling domain comprising the cytoplasmic tail of CD40. The present invention also relates to therapeutic uses thereof.

The present invention relates to a fusion protein comprising at least two cytokines, of which at least one is a modified cytokine with a strongly reduced binding affinity to its receptor, or to one of its receptors. Preferably, both cytokines are connected by a linker, preferably a GGS linker. The invention relates further to said fusion protein for use in treatment of diseases.

The disclosure provides Myxoma virus that expresses one or more immunomodulatory transgenes and its use in inhibiting and / or treating a hematological cancer in a subject. The disclosure also provides a leukocyte having a Myxoma virus that expresses one or more immunomodulatory transgenes and the use of the leukocyte for inhibiting and / or treating a hematological cancer in a subject.

A method of diagnosing an infectious disease, including determining the severity of the disease, in a subject comprising measuring an expression level of at least one protein selected from the group consisting of TSG-14, AGER, ANG-2 and ST2 in a sample of the subject; and diagnosing the disease based on said expression level. Kits for carrying out the diagnosis are also disclosed.

The presently disclosed subject matter relates to tumor infiltrated T cells induced by oncolytic virus ("OV-induced T cells"), methods of making and using said OV-induced T cells for an adoptive T-cell therapy. The presently disclosed subject matter further relates to oncolytic viruses and armed oncolytic viruses, methods of making and using said oncolytic viruses, as well as pharmaceutical compositions and kits comprising said oncolytic viruses.

The present invention relates to a cytokine trimer domain in which a first monomer, a second monomer (dimer) and a third monomer linked by a linker are bound by a knob-into-hole system, and an antibody prepared by replacing the constant region (Fc) of an antibody with the trimer domain, and a new type of fusion protein (Receptor-Antibody Conjugated (cell) Engager (RACE)) in which the cytokine trimer domain is bound. It has been confirmed that the RACE according to the present invention not only exhibits a binding ability to the target receptor superior to that of the parent antibody, but also exhibits excellent simultaneous binding ability to the antigen and the target receptor, and can be usefully used as a bispecific pharmaceutical composition.

The present disclosure relates to a tumor necrosis factor receptor 2 (TNFR2) agonist polypeptide comprising (i) a TNFR2 binding domain comprising three TNF homologous domains (THDs) that specifically bind to TNFR2; and (ii) an Fc domain. The present disclosure also relates to TNFR2 agonists for use in the treatment and / or prevention of e.g. Chronic pain or multiple sclerosis.

The invention discloses an application of a fat factor C1q / TNF (Tumor Necrosis Factor) associated protein 9 (CTRP-9) in enhancing T cell immunotherapy, and relates to a new application of the fat factor C1q / TNF associated protein 9 (CTRP-9) in regulating T cell functions, and the CTRP-9 is an immune regulation molecule secreted by fat tissues. According to the present invention, the CTRP-9 is exogenously supplemented, such that the effect intensity of the T cells in the anti-tumor immunoreaction can be effectively enhanced, and the activation and the proliferation of the T cells can be promoted; meanwhile, the CTRP-9 can also be used as a CAR-T cell enhancer, so that the immunotherapy effect is improved. The method can be applied to an immunotherapy system based on T cells, and provides a new regulation way and target for improving the T cell immunotherapy effect.

According to one aspect of the present invention, an oncolytic adenovirus vector for cancer treatment encoding at least TNFα and / or IL-2 is provided. The adenovirus vector is administered to a subject at least three times, preferably at least five, six, or seven times, in an active treatment cycle, with at least one administration, preferably the first, being systemic, and the active treatment cycle preferably does not include the administration of adoptive cell therapeutic compositions containing TIL or the administration of immune checkpoint inhibitors.

Disclosed herein are methods and compositions of RANKL-binding switch receptors and engineered immune cell comprising said switch receptors, wherein the switch receptor comprises a RANKL-binding ectodomain, transmembrane domain and a costimulatory endodomain.

The disclosure relates to adoptive cell therapy compositions including a population of isolated immune cells that are obtained from a donor subject. The immune cells can be modified to suppress Bruton's tyrosine kinase (BTK), interleukin-2-inducible T cell kinase (ITK), delta isoform of phosphoinositide 3-kinase (PI3Kδ), helios, blimp1, SOCS1, GATA3, IL-10, STAT3, TOX, CD25, foxp3, Ezh2, TGF-beta Receptor II, LAG-3, PD-1, TNF-alpha, or combinations thereof. The immune cells are optionally depleted of CD8+ T cells by about 10-fold or greater relative to un-depleted leukocytes.

An object of the present invention is to provide a method of evaluating intercellular interactions in neuroinflammation using a co-culture containing human-derived neural cells capable of mimicking human brain functions. According to the present invention, there is provided a method of evaluating intercellular interactions in neuroinflammation, the method including a step of producing a co-culture containing at least two cells selected from the group consisting of human-derived astrocytes, human-derived neurons, human-derived microglia, and human-derived oligodendrocytes, a step of applying an inflammatory stimulation to a first cell contained in the co-culture, a step of detecting at least one selected from the group consisting of an inflammatory response marker in the cells contained in the co-culture, neural activity of the cells, and cell morphology, and a step of evaluating, over time, a change in at least one selected from the group consisting of the inflammatory response marker, the neural activity, and the cell morphology in the first cell and a second cell different from the first cell contained in the co-culture.

This invention provides a recombinant transmembrane human tumor necrosis factor expressed in alfalfa. ‑α This method belongs to the field of biotechnology. This invention constructs a transmembrane human tumor necrosis factor... ‑α A plant binary expression vector for the gene is used, and then Agrobacterium-mediated transformation of the recipient alfalfa containing this plant binary expression vector is employed to prepare recombinant transmembrane human tumor necrosis factor. This invention utilizes alfalfa as a substrate plant for recombinant human tumor necrosis factor, providing a platform for recombinant transmembrane human tumor necrosis factor production. ‑α This provides an excellent cell system for expression, catering to the market demand for recombinant transmembrane trimeric tumor necrosis factor. ‑α This provides a new solution to the needs.

To provide a safe and effective mutated woodchuck post-transcriptional regulatory element (WPRE) for use in a retroviral vector.SOLUTION: Provided is a vector comprising a mutated woodchuck post-transcriptional regulatory element (WPRE), wherein the vector does not include an X protein promoter, and the mutated WPRE does not include an X protein open reading frame (ORF).SELECTED DRAWING: None

The present disclosure is directed to fusion proteins comprising a Tumor Necrosis Factor α (TNFα) binding protein and an interleukin-10 (IL-10) molecule, methods of making the fusion proteins, and methods of treating or preventing autoimmune and inflammatory conditions using the fusion proteins.

Disclosed are antigen-binding polypeptide complexes (e.g., antibodies and antigen-binding fragments thereof) having certain structural characteristics. Also disclosed are polynucleotides and vectors encoding such polypeptide complexes; cells, pharmaceutical compositions, and kits containing such polypeptide complexes; and methods of using such polypeptide complexes.

Described herein are compositions and methods for tissue-targeted expression of therapeutic genes, using AAV expression vectors that reduce the risk of toxicity associated with AAV gene therapy in the CNS by de-targeting the vulnerable neurons cells including the DRG cells on gene expression, and de-targeting the liver, a major suspect for over-expression in the periphery.