625 results about "L1" patented technology

The invention provides a lipidosome STING agonist delivery system based on a PD-L1 antibody as well as a preparation method and application of the lipidosome STING agonist delivery system, and belongs to the technical field of medical biology. Preparing lipidosome by adopting an ethanol injection method and an ammonium sulfate gradient technology; the PD-L1 antibody and the STING agonist can be loaded at the same time; the liposome is prepared by adopting an ethanol injection method and an ammonium sulfate gradient technology, and the STING agonist can be wrapped in the liposome in an active drug loading manner; dSPE-PEG2000-NHS and a PD-L1 antibody are mixed and incubated according to a specific proportion by utilizing a post-insertion method to form an antibody conjugated micelle, and the antibody conjugated micelle is fused with a blank liposome to realize antibody modification; secondly, the nano-liposome has good drug carrier characteristics and can effectively protect the loaded drug, reduce the risk of enzymolysis of the drug and improve the stability of the drug in vivo, so that the liposome drug delivery system simultaneously loading the nano-liposome and the nano-liposome is successfully prepared.

Multispecific antibody having a binding site for ICOS and a binding site for a second antigen, e.g., an immune checkpoint molecule such as PD-L1. Use of the multispecific antibody in immuno-oncology, including for treatment of solid tumours.

Provided are complementarity determining regions (CDRs) of the VHH chain of an anti-PD-L1 single domain antibody, wherein the CDRs of the VHH chain comprise the following: CDR1 having the amino acid sequence set forth in SEQ ID NO:5n+1; CDR2 having the amino acid sequence set forth in SEQ ID NO:5n+2, or a CDR2 having an amino acid sequence which has greater than 85% sequence identity to the sequence set forth in SEQ ID NO:2; and CDR3 having the amino acid sequence set forth in SEQ ID NO:5n+3, where each n is independently 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, or 15.

The invention relates to a combination of a binding agent comprising (i) a first binding region which binds to PD-1, PD-L1, or both and which antagonizes the PD-1 / PD-L1 interaction; and (ii) a second binding region which binds to VEGF, VEGF receptor (VEGFR), or both and which antagonizes the VEGF / VEGFR interaction, and an antibody-drug conjugate comprising an antibody or fragment thereof that specifically binds to a target expressed on the surface of a tumour cell.

Provided herein are compositions of NK-92™ cells that express a combination of PD-L1 CAR, CD16 and IL2, and the method of using these cells to to reduce tumor cells and cells in tumor microenvironment (e.g., MDSCs or TAMs) and treat cancer.

Provided herein are compositions of NK-92™ cells that express a combination of PD-L1 CAR, CD16 and IL2, and the method of using these cells to to reduce tumor cells and cells in tumor microenvironment (e.g., MDSCs or TAMs) and treat cancer.

Provided herein are novel anti-CD27 and anti-PD-L1 antibodies, and binding domains thereof, as well as bispecific constructs and anti-CD27 binding domain linked to an anti-PD-L1 binding domain. Also provided herein are methods of stimulating T cell activity, methods of inducing or enhancing an immune response, and methods of treating a disease or condition (e.g., cancer) by administering the bispecific constructs, antibodies, or antigen binding fragments thereof, or compositions described herein to a patient in need thereof.

The present application provides antibodies including antigen binding fragment thereof that specifically recognizing programmed cell death 1 ligand 1 (PD-L1). Also provided are methods of making and using these antibodies.

Provided are methods for treating cancer using local administration of certain CpG oligonucleotides (CpG ODN) and systemic administration of a checkpoint inhibitor such as an anti-PD-1 antibody, an anti-PD-L1 antibody, and / or an anti-CTLA-4 antibody. In preferred embodiments, the CpG ODN are selected based on their propensity to induce high amounts of interferon alpha (IFN-α) and T-cell activation relative to interleukin-10 (IL-10) and B-cell activation. In certain embodiments, the methods further include pretreatment with radiotherapy, to potentiate the combination immunotherapy.

The invention relates to the technical field of biological medicines, and discloses a PD-L1 K263 acetylation modified antibody, which is prepared from an immunogen containing a sequence as shown in SEQ ID NO.1. The PD-L1 K263 acetylation modified antibody is a PD-L1 K263 acetylation modified antibody. The invention also discloses a preparation method of the PD-L1 K263 acetylation modified antibody. The preparation method comprises the following steps: designing and synthesizing a polypeptide antigen, preparing an immunogen, immunizing animals, purifying the antibody and evaluating serum titer. The antibody provided by the invention can accurately recognize and combine with the PD-L1 protein subjected to K263 acetylation modification in the breast cancer, provides a specific tool for qualitative and quantitative detection of K263Ac-PD-L1 in the breast cancer, and provides a reliable molecular marker detection means for evaluating the curative effect of anti-PD-1 / PD-L1 immunotherapy; therefore, a biological preparation with specificity and practicability and a technical support are provided for accurate diagnosis, targeted therapy and curative effect monitoring of breast cancer.

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.

The application provides a preparation of a sema7A monoclonal antibody 8A12 and a treatment effect of the sema7A monoclonal antibody 8A12 on lupus nephritis, wherein the CDR-H1 of the heavy chain variable region of the monoclonal antibody 8A12 is an amino acid sequence shown in SEQ ID No. 1, the CDR-H2 of the heavy chain variable region is an amino acid sequence shown in SEQ ID No. 2, and the CDR-H3 of the heavy chain variable region is an amino acid sequence shown in SEQ ID No. 3; the CDR-L1 of the light chain variable region of the monoclonal antibody 8A12 is an amino acid sequence shown in SEQ ID No. 4, the CDR-L2 of the light chain variable region is an amino acid sequence shown in SEQ ID No. 5, and the CDR-L3 of the light chain variable region is an amino acid sequence shown in SEQ ID No. 6. The monoclonal antibody 8A12 can effectively inhibit the expression up-regulation of IL-1beta, TNF-alpha and IL-6 caused by Sema7A recombinant protein, can effectively inhibit the macrophage inflammatory response induced by Sema7A, and can continuously and effectively reduce serum anti-double-stranded DNA antibodies and kidney damage of lupus mice. The monoclonal antibody 8A12 can be used for preparing a pharmaceutical composition for preventing and / or treating systemic lupus erythematosus and / or lupus nephritis thereof.

The invention provides an anti-PD-1 antibody, a CAR-T cell, and a preparation method and application thereof. The anti-PD-1 antibody comprises LCDR-1-3 as shown in SEQ ID NO: 1-3 and HCDR-1-3 as shown in SEQ ID NO: 4-6, respectively. The CAR-T cell expresses a novel element for efficiently blocking the PD-1, and the element is a single-chain antibody for targeting the PD-1 in a cell membrane anchoring manner. And the chimeric antigen receptor and the cell membrane anchored anti-PD-1 scFv are connected by a 2A cleavage protein. The membrane anchor type anti-PD-1 scFv expressed by the CAR-T cell can almost completely block the expression of PD-1 on the surface of a T cell membrane, and further block a signal channel combined with PD-1 / PD-L1, so that the capability of T cell depletion caused by antagonism tumor of the CAR-T cell is enhanced, and the purpose of enhancing the anti-tumor effect of the CAR-T cell is achieved.

The invention belongs to the technical field of biological pharmacy, and relates to a bifunctional fusion protein targeting PD-1 / PD-L1 and IL-33 as well as a construction method and application of the bifunctional fusion protein. The bifunctional fusion protein comprises a PD-1 / PD-L1 antibody and a targeted IL-33 functional fragment, T cells are activated by blocking a PD-1 / PD-L1 signal to kill tumor cells, meanwhile, the level of IL-33 in tumor tissue is reduced, and the activity of IL-33 is inhibited. Researches show that the bifunctional fusion protein can increase infiltration of functional T cells, enhance T cell response and remodel a tumor microenvironment so as to generate an anti-tumor effect superior to that of combined treatment, and has a very good application prospect.

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.

The present invention relates to a single domain antibody against PD-L1 and its use. More specifically, a single domain antibody that specifically binds to PD-L1, an immune checkpoint protein, has been prepared, and its affinity to immune antigens and antitumor effect have been confirmed, so that the single domain antibody can be usefully used as an immune checkpoint inhibitor in immunotherapy.

Provided are combination therapies that include an inhibitor of PD-1 or PD-L1 and an antibody-drug conjugate targeting claudin 18.2.

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 invention relates to the technical field of biological medicines, in particular to a preparation method of an inhibitor targeting a MAX-PD-L1 promoter specific binding motif and a double-target inhibitor, through ChIP-seq and site-directed mutagenesis experiments, a core binding motif of MAX and a PD-L1 promoter, such as 5 '-CAC [GA] TG-3', is defined, it is ensured that the inhibitor only targets a key site of MAX-PD-L1 interaction, and the activity of the MAX-PD-L1 promoter specific binding motif is improved. The off-target effect is avoided, and a high-specificity target spot is provided for subsequent inhibitor design. The cell permeability of the DNA aptamer screened based on the specific binding motif is improved after cholesterol modification, and the affinity of the DNA aptamer is obviously higher than that of a traditional antibody. A small molecule compound virtually screened through a molecular docking model is optimized through hydrogen bond and hydrophobic interaction, and then the binding affinity with MAX is improved. After treatment with the inhibitor, the combination inhibition rate of MAX and the PD-L1 promoter is high, the transcriptional activity of PD-L1 is obviously reduced, the killing rate of T cells to tumor cells is also improved, and immune escape is effectively blocked.

The invention belongs to the field of biological medicine, and discloses a membrane binding type IL7 fusion protein, an engineered immune cell for expressing the membrane binding type IL7 fusion protein and application of the membrane binding type IL7 fusion protein. The fusion protein comprises an IL7 region and a transmembrane domain and can be expressed on a cell membrane, the tumor cell killing ability and the T cell survival ability of T cells expressing the fusion protein are both enhanced, and the aims of improving the tumor immune cell treatment effect and reducing the toxic and side effects are achieved. Particularly, the IL7 fusion protein anchors and expresses IL7 on the surface of a cell through transmembrane domains such as CD80 or PD-L1 and the like, so that (1) immune cells can be accurately regulated and controlled, the possibility that an excessive IL7 signal possibly causes autoimmune response or aggravates CRS is reduced, and the safety of the IL7 to immune cells such as T cells and the like is enhanced; (2) the half-life period of IL7 is prolonged, and the anti-tumor effect of adoptive immune cells is enhanced; and (3) the transmembrane fragment is linked with the IL7 through a hinge region of the flexible linker G4S, CD80 or PD-L1, so that the flexibility of the IL7 is enhanced, and the proliferation and killing functions of the IL7 on T cells are enhanced.

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 invention discloses a protein drug loaded GelMA microsphere, a preparation method and application thereof, the protein drug loaded GelMA microsphere comprises a GelMA microsphere and a protein drug loaded on the GelMA microsphere, and the protein drug is composed of albumin paclitaxel and alphaPD-L1. The drug carrier is loaded with albumin paclitaxel and the alphaPD-L1 antibody, so that synergistic treatment can be realized, and the cancer treatment effect is improved; gelMA is used as a drug carrier, albumin paclitaxel and an alphaPD-L1 antibody are delivered, and the drug-loaded GelMA microspheres are injected into tumor tissues in situ, so that the targeting property and bioavailability of the drug can be effectively improved, side effects are reduced, the drug is enriched in a focus, and the circulating drug concentration is reduced.

The invention belongs to the technical field of biological medicine, and particularly relates to a single-domain antibody VHH-L1 targeting LINGO-1 protein, and the amino acid sequence of the single-domain antibody VHH-L1 is shown as SEQ ID NO: 1. The single-domain antibody has nanomole-level high affinity and excellent specificity, can effectively block the interaction between LINGO-1 and ligands thereof, and remarkably promotes differentiation and myelination of oligodendroglia cells. The invention further provides a neural stem cell subjected to genetic engineering modification, and the neural stem cell can stably and continuously secrete the single-domain antibody VHH-L1. In a spinal cord injury animal model, the engineered stem cell shows an excellent treatment effect, can significantly promote motor function recovery, axon regeneration and myelin sheath repair, and effectively inhibits glial scar formation. The double advantages of cell therapy and long-acting protein delivery are fused, and a brand new efficient treatment strategy is provided for demyelination diseases such as multiple sclerosis and spinal cord injury.

A conditionally active bispecific antibody comprising: an IgG antibody or antibody fragment that binds to human EpCAM protein, the IgG antibody or antibody fragment comprising a light chain variable region having three complementarity-determining regions L1, L2, and L3, and a heavy chain variable region having three complementarity-determining regions H1, H2, and H3; and at least one scFv antibody fragment that binds to a T lymphocyte protein linked to the C-terminus of at least one light chain of the IgG antibody or antibody fragment.