883 results about "L1" patented technology

The disclosure provides a method for immunotherapy of a subject afflicted with cancer, comprises administering to the subject a composition comprising a therapeutically effective amount of an antibody that inhibits signaling from the PD-1 / PD-L1 signaling pathway. This disclosure also provides a method for immunotherapy of a subject afflicted with cancer comprising selecting a subject that is a suitable candidate for immunotherapy based on an assessment that the proportion of cells in a test tissue sample from the subject that express PD-L1 on the cell surface exceeds a predetermined threshold level, and administering a therapeutically effective amount of an anti-PD-1 antibody to the selected subject. The invention additionally provides rabbit mAbs that bind specifically to a cell surface-expressed PD-L1 antigen in a FFPE tissue sample, and an automated IHC method for assessing cell surface expression in FFPE tissues using the provided anti-PD-L1 Abs.

This disclosure provides novel bispecific antibodies that specifically bind to CD47 and Programmed Death-Ligand 1 (PD-L1). The disclosure further relates to methods of making the bispecific antibodies and nucleic acids encoding the antibodies. The disclosure further relates to therapeutic methods for use of the bispecific antibodies in the treatment of a condition associated with malignant cells expressing CD47 and / or PD-L1.

The disclosure provides a method for immunotherapy of a subject afflicted with cancer, comprises administering to the subject a composition comprising a therapeutically effective amount of an antibody that inhibits signaling from the PD-1 / PD-L1 signaling pathway. This disclosure also provides a method for immunotherapy of a subject afflicted with cancer comprising selecting a subject that is a suitable candidate for immunotherapy based on an assessment that the proportion of cells in a test tissue sample from the subject that express PD-L1 on the cell surface exceeds a predetermined threshold level, and administering a therapeutically effective amount of an anti-PD-1 antibody to the selected subject. The invention additionally provides rabbit mAbs that bind specifically to a cell surface-expressed PD-L1 antigen in a FFPE tissue sample, and an automated IHC method for assessing cell surface expression in FFPE tissues using the provided anti-PD-L1 Abs.

The disclosure provides a method for immunotherapy of a subject afflicted with cancer, comprises administering to the subject a composition comprising a therapeutically effective amount of an antibody that inhibits signaling from the PD-1 / PD-L1 signaling pathway. This disclosure also provides a method for immunotherapy of a subject afflicted with cancer comprising selecting a subject that is a suitable candidate for immunotherapy based on an assessment that the proportion of cells in a test tissue sample from the subject that express PD-L1 on the cell surface exceeds a predetermined threshold level, and administering a therapeutically effective amount of an anti-PD-1 antibody to the selected subject. The invention additionally provides rabbit mAbs that bind specifically to a cell surface-expressed PD-L1 antigen in a FFPE tissue sample, and an automated IHC method for assessing cell surface expression in FFPE tissues using the provided anti-PD-L1 Abs.

The invention provides application of TRMT61A and its inhibitor tetramethylthiuram disulfide in tumor immunotherapy, and relates to the technical field of biological medicine, clinical research proves that RNA m1A methyltransferase TRMT61A is highly expressed in tumor tissues and is related to poor prognosis of tumor patients, and can be used as one of tumor therapy targets. Meanwhile, high expression of the TRMT61A is related to poor prognosis of a tumor patient receiving anti-PD-1 immunotherapy, and after anti-PD-1 antibody immunotherapy is carried out on the patient with low TRMT61A expression level in the tumor of the patient, pathological complete relief is easier. Tetramethylthiuram disulfide inhibits TRMT61A, inhibits m1A modification regulation of TRMT61A on PD-L1 mRNA, increases PD-L1 protein expression, and is combined with a PD-1 antibody drug to significantly enhance the immunotherapy effect of the anti-PD-1 immune checkpoint drug in treating malignant tumors.

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.

The present invention relates to a hetero (aromatic) ring-substituted cyclic diamine compound, the preparation thereof and the use thereof in the preparation of a drug for treating and / or preventing tumors. The structural formula of the compound is as shown in (I). The compound has a significant inhibitory effect on the growth of cells of tumors such as leukemia, lymphoma, breast cancer, melanoma, ovarian cancer, colorectal cancer, cervical cancer, lung cancer, prostate cancer, esophageal cancer, glioma, kidney cancer, nasopharyngeal carcinoma, liver cancer, gastric cancer and pancreatic cancer. Compared with the prior art, the compound of the present invention has a broad-spectrum anti-tumor activity, has a good effect on inhibiting tumors, and has an effect of degrading PD-L1 proteins, and is thus a PD-L1 immunomodulator.

Provided is a compound for double targeting of a fibroblast activation protein and an integrin subtype, comprising: (i) a chelating ligand moiety (CL); (ii) a first targeting moiety (BT); and (iii) a second targeting moiety (CY), wherein (i), (ii), and (iii) are fixed, combined, or connected by means of any L; BT is a fibroblast activation protein (FAP)-specific binding ligand structure; CY is an integrin subunit αvβ3 or αvβ6-specific binding ligand structure; L is selected from one or a combination of L1, L2, L3, L4, L5, L6, and L7; L1, L2, L3, L4, L5, L6, and L7 are each independently a key, a monovalent joint, a divalent joint, or a trivalent joint. Also provided are a preparation method for the compound and use thereof.

The present disclosure provides recombinantly manufactured fusion proteins comprising a Programmed Death-Ligand 1 (PD-L1) protein fragment or an analog thereof linked to a canine Fc fragment. Embodiments include the administration of the fusion proteins to patients as a treatment for cancers, tumors or other diseases associated with expression of the PD-L1 protein in dogs. Exemplary Fc fusion proteins and pharmaceutical formulations of exemplary Fc fusion proteins are provided, in addition to methods of use and preparation.

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.

The invention discloses an anti-CD3D antibody and application thereof.The antibody comprises a heavy chain variable region and a light chain variable region, the amino acid sequence of CDR-H1 of the heavy chain variable region is shown as SEQ ID NO: 4, the amino acid sequence of CDR-H2 of the heavy chain variable region is shown as SEQ ID NO: 5, and the amino acid sequence of CDR-H3 of the heavy chain variable region is GDL; the amino acid sequence of the CDR-L1 of the light chain variable region is as shown in SEQ ID NO: 6, the amino acid sequence of the CDR-L2 of the light chain variable region is as shown in SEQ ID NO: 7, and the amino acid sequence of the CDR-L3 of the light chain variable region is as shown in SEQ ID NO: 8. The anti-CD3D antibody is a rabbit monoclonal antibody, the obtained antibody is high in titer, clear in specific positioning in immunohistochemical staining and free of non-specific background staining, the antibody is wide in application, and the antibody can be used in pathological immunohistochemical staining experiments and can also be used in Western blot and flow cytometry experiments.

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.

The invention provides a functional fragment, a ubiquitin carboxyl terminal hydrolase L1 antibody and application thereof, and belongs to the technical field of antibodies. The functional fragment comprises a complementary determining region Ab1 and a complementary determining region Ab2, wherein the Ab1 comprises CDR-VL1, CDR-VL2, CDR-VL3, CDR-VH1, CDR-VH2 and CDR-VH3, and the Ab2 comprises CDR-VL1, CDR-VL2, CDR-VL3, CDR-VH1, CDR-VH2 and CDR-VH3; and the Ab2 comprises a CDR-VL1, a CDR-VL2, a CDR-VL3, a CDR-VH1, a CDR-VH2 and a CDR-VH3. The invention provides an antibody for specifically recognizing ubiquitin carboxyl terminal hydrolase L1 (Uch-L1), which has the characteristics of high specificity and high affinity, is suitable for quantitative or qualitative detection of Uch-L1, effectively reduces the detection cost of Uch-L1, shortens the detection time, improves the detection efficiency, and can realize sensitivity, stability and high sensitivity required by rapid diagnosis. And general standards such as economy and no equipment are needed.

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 disclosure provides a method for treating a subject afflicted with a tumor comprising administering to the subject a therapeutically effective amount of an anti-PD-1 antibody or antigen-binding portion thereof or an anti-PD-L1 antibody or anti-gen-binding portion thereof, wherein the subject is identified as having a high inflammatory gene signature score. In some embodiments, the high inflammatory gene signature score is determined by measuring the expression of a panel of inflammatory genes in a tumor sample obtained from the subject, wherein the inflammatory gene panel comprises CD274 (PD-LI), CD8A, LAG3, and STAT1.

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.

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 belongs to the field of preparation of biomedical nano-materials, and particularly relates to a tumor microenvironment responsive bacterium-nano hybrid system as well as a preparation method and application thereof. According to the invention, an engineering bacterium containing an acid response promoter and coding PD-L1 blocking peptide is prepared, and then lipidosome nanoparticles containing calcium carbonate, curcumin and an XIAP / cIAP1 antagonist are attached to the bacterium, so that the bacterium-nano hybrid system with tumor microenvironment response is obtained. The system can realize accurate drug delivery and controllable release in an acidic tumor microenvironment through a unique pH response mechanism, shows remarkable tumor targeting and treatment effects, and can be used as an anti-tumor drug.

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 relates to an SR-B1 targeted polypeptide compound and application thereof in preparation of antitumor drugs and immunotherapy sensitizers, and belongs to the technical field of biological drug manufacturing. In order to solve the problems that an existing PD-L1 inhibitor is single in action mechanism and immune system dysfunction is easily caused, the invention provides an SR-B1 targeted polypeptide compound which is composed of SR-B1 targeted polypeptide and Resiquimod. The SR-B1 targeting polypeptide comprises an SR-B1 targeting peptide fragment, a self-assembly peptide fragment and a hydrophobic molecule which are connected in sequence. The SR-B1 targeting polypeptide can recognize overexpressed SR-B1 in tumor cells, block cholesterol uptake, inhibit tumor progression and inhibit expression of PD-L1 at the same time. The polypeptide compound accurately delivers Resiquimod to a tumor site, anti-tumor immune response is activated, and sensitivity of tumor immunotherapy is greatly enhanced through combination of cholesterol metabolism regulation and immunotherapy.

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.