136 results about "L1" patented technology

The present application provides an antibody binding to human PD-L1, and a tetravalent bispecific antibody of anti-PD-1 and PD-L1 constructed based on the antibody binding to human PD-L1. The tetravalent bispecific antibody of the present application does not need to be subjected to Fc modification, does not produce mismatch problems, has a simple preparation method, and has similar or even better biological activity and physicochemical properties than monoclonal antibodies.

Therefore, this disclosure provides a genetically engineered mesenchymal stem cell (MSC) population, including an expression vector containing the Akt or HGF gene and the PD-L1 gene. It also provides a method for synergistically improving the survival status and immunomodulatory capacity of mesenchymal stem cells or enhancing their proliferation, including transfecting mesenchymal stem cells with the Akt or HGF gene and the PD-L1 gene; and a method for preventing, improving, and / or treating ischemic conditions, enhancing neurogenesis, or reducing neuronal death, including administering an effective amount of the genetically engineered mesenchymal stem cell population of this disclosure to individuals in need.

The disclosure provides a method for treating a subject afflicted with a tumor, e.g., derived from a non-small cell lung cancer (NSCLC), comprising administering to the subject a combination of a (a) chemotherapy, (b) an anti-PD-1 antibody or an anti-PD-L1 antibody, and (c) an anti-CTLA-4 antibody, wherein the chemotherapy is administered for a period of time that is less than the standard.

Therapeutic use and dosing regimen of anti-ICOS antibodies or antigen-binding fragments thereof for modulating the ratio between regulatory T cells and effector T cells, stimulating the immune system of patients, and / or treating tumours or cancers, as monotherapy or combination therapy, e.g., with anti-PD-L1 antibodies or antigen-binding fragments thereof.

The application discloses a LYTAG-Gem compound for enhancing the anti-tumor effect of gemcitabine and application thereof, relates to the technical field of biological medicine, and particularly relates to a gemcitabine (Gem) targeted delivery system based on a lysosome targeting chimera (LYTAC) and application thereof in enhancing the anti-tumor process. 2+ The system is assembled from heavy chain ferritin, Ni 2+ , NTA-PEG5000-DBCO and a targeting ligand TPP-1-N3 in a specific mass percentage, can efficiently load Gem and form a nano compound with a particle size of about 59-79 nm, the system targets tumor cells through heavy chain ferritin, and realizes site-specific release of Gem in cells by means of an endocytosis-lysosome pathway mediated by the LYTAC structure, in-vivo pharmacodynamic experiments show that the LYTAC-Gem compound can significantly inhibit the tumor growth of a KPC pancreatic cancer mouse model, molecular mechanism research further reveals that the LYTAC-Gem compound can down-regulate the expression of PD-L1 protein in tumor tissues, and it is indicated that the LYTAC-Gem compound has the potential to activate an anti-tumor immune response, and the application provides a novel targeted delivery strategy for overcoming the toxic side effects and tumor drug resistance of gemcitabine.

The application discloses a recombinant oncolytic virus targeting CD317 gene and application thereof in anti-tumor, and belongs to the technical field of tumor treatment. The recombinant oncolytic virus comprises a CD317 inhibitor and an oncolytic virus, and is formed by integrating the CD317 inhibitor into the oncolytic virus genome. The CD317 inhibitor is a substance capable of inhibiting CD317 gene expression or targeting degradation of CD317 protein function, and is selected from shRNA or siRNA targeting CD317. The application develops the oncolytic virus targeting knockdown of CD317 expression, inhibits tumor cell proliferation by reducing CD317 expression of tumor cells, reduces PD-L1 expression so as to break the immune escape mechanism, simultaneously enhances the killing sensitivity of tumor cells to CD8+ T cells, forms a synergistic effect with the oncolysis of the oncolytic virus, and the recombinant oncolytic virus has stronger in-vivo anti-tumor activity, thereby providing a new potential scheme for CD317-driven tumor treatment.

Provided is an anti-PD-L1 antigen binding protein, capable of binding to primate-derived PD-L1 with a KD value of 1×10−8 M or less. The antigen binding protein can block the binding of PD-1 and CD80 to PD-L1, stimulate the secretion of cytokines in immune cells, and can inhibit tumor growth and / or tumor cell proliferation. Also provided is a fusion protein, comprising human TGFBRII or a fragment thereof and the antigen binding protein. Also provided is an application of the antigen binding protein and / or the fusion protein in the prevention and treatment of tumors or cancers.

Pharmaceutical compositions and therapeutic methods are provided comprising a single-domain antibody consisting of SEQ ID NO:1 and a pharmaceutically acceptable carrier. The antibody inhibits KRAS GTPase activity and inhibits phosphorylation of STAT3. In certain embodiments, inhibition of KRAS results in decreased phosphorylation of ERK1 / 2. The antibody reduces tumor cell surface PD-L1 expression and reduces VEGF production. The antibody crosses the blood-brain barrier following systemic administration and may exhibit sustained biological activity in vivo. Methods are provided for treating KRAS-mutant cancers, including pancreatic cancer and triple negative breast cancer, and for enhancing anti-tumor immunity through reduction of PD-L1 expression.

Provided herein are binding molecules that bind to programmed cell death protein 1 (PD-1). Such binding molecules block the interaction between PD-1 and programmed death-ligand 1 and 2 (PD-L1 and PD-L2). Also provided herein are methods of using such binding molecules for preventing and treating cancer.

The present invention provides a bispecific antibody comprising a first portion targeting PD-L1 and a second portion targeting IL-1, wherein the first portion comprises an anti-PD-L1 antibody or its antigen-binding fragment, and the second portion comprises the extracellular binding domain of the IL-1 receptor (IL-1R) or a variant thereof, or an anti-IL-1β antibody or its antigen-binding fragment. The invention also provides the use of the bispecific antibody in the treatment of tumors.

Compositions related to synthetic PD-L1 peptides, chimeric PD-L1 peptides, and anti-PD-L1 antibodies, and methods for treating cancer, autoimmune diseases and Alzheimer's disease using said peptides or antibodies are disclosed.

The present application relates to a kind of based on chemotactic factor CXCL12 mutant modification double specific fusion protein and its application as immune checkpoint molecule targeted degradation platform in tumor immunotherapy, belong to biological medicine field.The specific problem of the present application is how to effectively enhance the effect of tumor immunotherapy, especially solve the problem of immune escape phenomenon in tumor microenvironment in traditional immunotherapy.To this end, the present application proposes a new KineTAC targeted degradation platform, specifically designs a new chemotactic factor CXCL12 and target protein binding polypeptide (such as anti-PD-1 / PD-L1 monoclonal antibody, anti-LAG-3 monoclonal antibody, etc.) Fusion expression protein molecule, enhance its binding affinity with receptor CXCR4 and CXCR7, and avoid stimulating tumor cell growth proliferation.The fusion protein can target and degrade the immunosuppressive molecules on the surface of tumor cells and immune cells, thereby enhancing the immune response of immune cells and improving the anti-tumor effect.

Provided herein are combination therapies for the treatment of cancer. In particular, the disclosed methods are directed to treatment of cancer in a patient comprising administering an antibody that blocks the interaction between PD-1 and PD-L1 and an FGFR inhibitor, wherein the antibody that blocks the interaction between PD-1 and PD-L1 and the FGFR inhibitor are administered if one or more FGFR variants are present in a biological sample from the patient.

This invention relates to the use of PD-L1 binding molecules in improving the stability of protein-drug conjugate formulations. It also relates to a pharmaceutical composition comprising a PD-L1 binding molecule and a protein-drug conjugate, and discloses its antitumor use.

The application discloses a biomaterial related to DCLK1 and application of DCLK1 in reversing an immunosuppressive microenvironment after EGFR-TKI drug resistance of lung adenocarcinoma, and belongs to the technical field of biotechnology.The biomaterial is an RNA molecule for inhibiting or reducing or down-regulating expression of a coding gene of a protein, or an RNA molecule for inhibiting or reducing or down-regulating activity or content of the protein, or an RNA molecule for knocking out a coding gene of the protein, or a coding gene, an expression cassette and the like related to the foregoing RNA molecule.The application shows through experiments that targeting DCLK1 can inhibit a GAS6 / AXL pathway, and down-regulate expression of PD-L1 and IDO1, thereby recovering T cell infiltration and proliferation capacity, reversing an immunosuppressive microenvironment after drug resistance, and indirectly suppressing progression of lung adenocarcinoma with three generations of EGFR-TKI drug resistance.

This invention belongs to the field of nanocarrier and immunotherapy technology, specifically relating to a lipid nanoparticle targeting tumor-associated macrophages, a combined delivery method, and its application in tumor immunotherapy. The lipid nanoparticles targeting CD206 tumor-associated macrophages constructed in this invention are used for efficient in vivo delivery of multifunctional nucleic acid molecules, achieving immune regulation, gene editing, and anti-tumor therapy. This invention achieves targeted delivery and multifunctional synergistic effects through lipid particle design, nucleic acid sequence design, and in vitro and in vivo functional verification. Through in vivo delivery of ipLNPs, macrophages can simultaneously achieve: 1) expression of anti-PD-L1 antibodies, blocking immunosuppressive signals; 2) expression of HER2-CAR structures, enhancing phagocytosis and killing ability against tumors; and 3) remodeling of the tumor immune microenvironment through CRISPR / Cas9-mediated FN1 knockout. The lipid nanoparticles constructed using this invention can solve the problem of insufficient targeting of immune cells in the tumor microenvironment by traditional LNP delivery systems.

This disclosure provides a method for treating a cancer patient comprising administering to the patient a therapeutically effective amount of an anti-PD-1 antagonist, for example, an anti-PD-1 or anti-PD-L1 antibody, in combination with an indolamine 2,3-dioxygenase inhibitor, wherein the patient is identified as exhibiting a combined biomarker comprising (a) a high IFNγ inflammatory signature score and (b) a low tryptophan 2,3-dioxygenase 2 (TDO2) gene expression score. The high IFNγ inflammatory signature score is determined by measuring the expression of a panel of IFNγ-related inflammatory genes in a cancer sample obtained from the patient, wherein the gene panel comprises, for example, IFNγ, CXCL10, CXCL9, HLA-DRA, IDO1, and STAT1. In some respects, the gene panel also includes CCR5, CXCL11, GZMA, and PRF1.In some aspects, the genetic panel comprises CXCR6, TIGIT, PD-L1, PD-L2, LAG3, NKG7, PSMB10, CMKLR1, CD8A, IDO1, CCL5, CXCL9, HLA.DQA1, CD276, HLA.DRB1, STAT1, HLA.E and TDO2.

The disclosure provides a method for treating a subject afflicted with a cancer comprising administering to the subject a therapeutically effective amount of an anti-PD-1 antagonist, e.g., an anti-PD-1 or anti-PD-L1 antibody, in combination with an indoleamine 2,3-dioxygenase inhibitor, wherein the subject is identified as exhibiting a combined biomarker comprising (a) a high IFNγ inflammatory signature score and (b) a low tryptophan 2,3-dioxygenase 2 (TDO2) gene expression score. The high IFNγ inflammatory signature score is determined by measuring the expression of a panel of IFNγ related inflammatory genes in a cancer sample obtained from the subject, wherein the gene panel comprises, e.g., IFNγ, CXCL10, CXCL9, HLA-DRA, IDO1, and STAT1. In some aspects, the gene panel further comprises CCR5, CXCL11, GZMA, and PRF1. In some aspects, the gene panel comprises CXCR6, TIGIT, PD-L1, PD-L2, LAG3, NKG7, PSMB10, CMKLR1, CD8A, IDO1, CCL5, CXCL9, HLA.DQA1, CD276, HLA.DRB1, STAT1, HLA.E, and TDO2.

The application discloses a double-drug self-enhanced layered double hydroxide nanosystem and application thereof. The iron-ruthenium layered double hydroxide in the nanosystem has double enzyme activity, can efficiently catalyze H2O2 to generate O2 and active oxygen in a tumor microenvironment, significantly relieves hypoxia while inducing oxidative stress, the MCT4 specific inhibitor VB124 in the system creates an acidic microenvironment by blocking lactic acid output, amplifies the catalytic efficiency of FeRu, and establishes a self-enhanced catalytic effect; and the co-loaded epigenetic regulator JQ1 down-regulates the expression of PD-L1 by inhibiting BET protein. The system amplifies the catalytic efficiency of FeRu, significantly induces ferroptosis, reverses the immunosuppressive microenvironment with the help of epigenetic regulation, induces the release of damage-associated molecular patterns, causes the infiltration of immune cells, and finally cooperatively triggers a strong anti-tumor immune response. The self-enhanced catalysis-epigenetic regulation synergistic strategy realized by the system provides an innovative solution for improving the effect of tumor immunotherapy.

The present application discloses immune effector cells expressing extracellular PD-L1 binding domain CAR and linking secretory interferon fusion protein and application methods thereof. The protein construct involved in the immune effector cells includes: (a) a chimeric antigen receptor (CAR) containing a PD-L1 binding domain; and (b) a secretory fusion protein containing IFN. The protein construct stimulates tumor cells to increase the expression amount or frequency of PD-L1, thereby further enhancing the killing ability of PD1-CAR-T cells on target cells and more effectively inhibiting or killing tumor cells.

Provided are antibodies or fragment thereof having binding specificity to the human chemokine (C-C motif) receptor 8 (CCR8) protein, used alone or in combination with a PD-1 or PD-L1 inhibitor for the treatment of cancer.

Radiolabeled anti-PD-L1 antibodies and their use in immuno-PET imaging are provided herein. Included are methods of detecting the presence of PD-L1 proteins in a patient or sample.

The present invention provides novel anti-PD-L1 antibodies and antibody-drug conjugates and methods of using such anti-PD-L1 antibodies and antibody-drug conjugates to treat cancer.

This invention belongs to the field of biotechnology, specifically relating to a high-affinity anti-tumor NK cell, its preparation method, and its application. This invention designs NK92 cells transfected with a haPD1 high-affinity chimeric conversion receptor, wherein the high-affinity chimeric conversion receptor includes the extracellular segment of haPD-1, the transmembrane segment of CD28, the intracellular segment of DAP10, and the intracellular segment of CD3ζ. This invention prepares haChR3-NK92 cells through the construction of a recombinant lentiviral vector, lentiviral packaging, and lentiviral transfection of NK92 cells. In this invention, haPD-1 serves as the extracellular recognition domain of the CAR structure, specifically binding to PD-L1 on tumor cells to achieve a stronger tumor-killing effect. The co-stimulatory molecule CD28 serves as the transmembrane region to transmit extracellular information into the cell, integrating the adaptor protein DAP10 of the NK cell surface activator receptor NKG2D into the cell, and further embedding the intracellular segment CD3ζ commonly used in CAR design to jointly promote NK cell activation. The preparation method of this invention can successfully construct haChR3-NK92 cells, achieve the expression of the target plasmid, and be applied in anti-tumor drug research.

Small interfering RNAs inhibiting the programmed cell death ligand 1 (PD-L1) and the use thereof. Sense strands of the small interfering RNAs (siRNAs) have a length of 18-22 bases, and the siRNAs specifically pair with a specific region of a target gene. The siRNAs have the following uses: (1) treating cancer which involves high PD-L1 expression; or (2) inhibiting the expression of PD-L1 protein.

The present disclosure relates generally to antibodies and functional binding fragments thereof that bind to programmed death-ligand 1 (PD-L1). In particular, the disclosed antibodies and fragments bind to human PD-L1 and comprise novel complementary determining regions (CDRs) also disclosed herein. Finally, the present disclosure relates to administering the disclosed antibodies and fragments to subjects with cancer, thereby treating or slowing the progression or proliferation of the cancer.

This invention discloses a nanocomposite loaded with PD-L1 siRNA and an anti-tumor peptide, its preparation, and its application in treating renal cell carcinoma. The nanocomposite uses a dendritic macromolecule as its carrier, and the loaded peptide is Tat-HSPB1, whose amino acid sequence is shown in SEQ ID NO.1. The amino acid sequence of the loaded PD-L1 siRNA is shown in SEQ ID NO.2. The composite of this invention utilizes multiple interactions between phenylboronic acid, nucleic acids, and peptides to achieve stable co-assembly and acid-responsive intracellular release. While reducing the cytotoxicity of high-generation dendritic macromolecules, it effectively delivers siPD-L1 to specifically downregulate PD-L1 expression in renal tumor cells, thereby relieving tumor immunosuppression. Synergistically, with the anti-tumor activity of Tat-HSPB1 itself, this composite can significantly induce tumor cell death and inhibit its proliferation, providing a novel, highly efficient, and low-toxicity strategy for renal cell carcinoma immunotherapy.

The present invention provides anti-PD-L1 antigen binding molecules, including antibodies and the antigen binding fragment thereof, and methods for using the same for treating a variety of diseases, including cancers.