1075 results about "L1" patented technology

The present invention belongs to the field of biological detection technology, and specifically relates to an anti-monkey C-reactive protein monoclonal antibody, an enzyme-linked immunosorbent assay kit and its application. Named CRP-13, CRP-13 includes a heavy chain variable region and a light chain variable region; the heavy chain variable region has three complementary determining regions CDR-H1 to CDR-H3, and the amino acid sequences are shown in SEQ ID NO.6-SEQ ID NO.8; the light chain variable region has three complementary determining regions CDR-L1 to CDR-L3, and the amino acid sequences are shown in SEQ ID NO.9-SEQ ID NO.11. The monoclonal antibody of the present invention can specifically bind to monkey C-reactive protein with high specificity. The above monoclonal antibody can be used to screen a paired monoclonal antibody, and a monkey C-reactive protein enzyme-linked immunosorbent assay kit is obtained based on the combination of the monoclonal antibodies, which can detect the content of monkey C-reactive protein in monkey serum, plasma or tissue fluid.

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 relates to a polypeptide ligand and a derivative of E3 ubiquitin ligase as well as a preparation method and application of the polypeptide ligand and the derivative, and relates to the technical field of biological medicines. The polypeptide ligand of the E3 ubiquitin ligase is characterized in that the amino acid sequence of the polypeptide ligand is shown as any one of SEQ ID NO: 1-3, and at least one disulfide bond is formed between cysteine residues in the amino acid sequence of the polypeptide ligand; the polypeptide ligand is combined with the E3 ubiquitin ligase RNF43 and / or the E3 ubiquitin ligase ZNRF3. The polypeptide ligand provided by the invention can be used for flexibly and modularly constructing various bifunctional molecules, such as small-size bifunctional molecules or bifunctional molecules with components which cannot be obtained through expression, so as to degrade disease-related membrane proteins, such as PD-L1, EGFR and the like, and has the potential of disease treatment.

The invention discloses an anti-PD-L1 antibody coupling drug and a preparation method thereof, belongs to the field of biological medicines, and is used for preparing anti-cancer drugs. The antibody coupling medicine is formed by coupling an anti-PD-L1 antibody and a payload through a linker, a light chain variable region sequence of the antibody is a sequence recorded by SEQ ID NO: 1, a heavy chain variable region sequence of the antibody is a sequence recorded by SEQ ID NO: 2, the payload is an avixatecan derivative Dxd, and the ratio (DAR) of the payload to the antibody is 6-8. The antibody-conjugated drug has a better killing effect on PD-L1 positive tumor cells of human and dogs, and has fewer dimers and higher thermal stability at a high DAR value (DAR6-8), and an accelerated stability test shows that the antibody-conjugated drug has good structural stability and binding activity.

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 a tumor exosome (TDEs) fluorescence detection method based on tandem hybrid chain reaction (HCR) and selective coordination, and aims to combine an aptamer, a tandem enzyme-free amplification technology and selective coordination of Cu < 2 + > to analyze a clinical lung cancer blood sample. The programmed cell death ligand 1 (PD-L1) biomarker overexpressed on the surface of the TDEs is selected as a target for detecting the exosome. The HCR can easily generate a large amount of double-stranded DNA, so that the HCR can be used as a means for signal amplification. The high affinity of the aptamer to the protein will affect the tandem HCR reaction and then modulate the HCR product. Cu < 2 + > and a double-stranded DNA product are utilized to form a compound, and a fluorescence signal of calcein can be accurately adjusted, so that accurate fluorescence quantification is performed on the concentration of TDEs.

The invention discloses preparation and application of a targeting LYPD3 chimeric antigen receptor T cell. The chimeric antigen receptor comprises an LYPD3 antigen binding domain, a transmembrane domain, a costimulatory signal transduction domain and an intracellular signal transduction domain, the LYPD3 antigen binding domain comprises a heavy chain variable region with CDR-H1, CDR-H2 and CDR-H3 and a light chain variable region with CDR-L1, CDR-L2 and CDR-L3, and the CDR-H1, the CDR-H2 and the CDR-H3 are respectively composed of amino acid sequences of SEQ ID NO: 3, SEQ ID NO: 4 and SEQ ID NO: 5. And the CDR-L1, the CDR-L2 and the CDR-L3 are respectively composed of amino acid sequences as shown in SEQ ID NO: 6, SEQ ID NO: 7 and SEQ ID NO: 8.

The invention discloses a typing analysis method for extracellular vesicles secreted by tumor cells and immune cells, which comprises the following steps: designing a PD-L1 protein recognition aptamer PD-L1-L, an EpCAM protein recognition aptamer EpCAM-L and a molecular beacon according to different expression levels of surface markers of the extracellular vesicles (PD-L1 + and EpCAM +) derived from the tumor cells and the extracellular vesicles (PD-L1 + and EpCAM-) derived from the immune cells; when the DNA probe recognizes the extracellular vesicles, fluorescence of the Cy5-PD-L1-L aptamer of the tumor cell source extracellular vesicles is quenched, a fluorescence signal of the Connector is recovered, and the immune cell source extracellular vesicles do not respond, so that the two extracellular vesicles are subjected to typing analysis. The method has the advantages that the extracellular vesicles of different cell sources can be subjected to typing analysis by using a strategy based on double aptamers and double switches, and false positive signals caused by single aptamer recognition are avoided.

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 invention relates to a multifunctional silica plastid integrating chemotherapy, immunotherapy and gas therapy, and relates to a preparation method of the multifunctional silica plastid and application of the multifunctional silica plastid in tumor diagnosis and treatment. The schematic diagram is as shown in the figure, the membrane components comprise conventional phospholipid and complex lipid, a chemotherapeutic drug doxorubicin (DOX) entrapped on a hydrophilic core and Fe3 (CO) 12 entrapped on a hydrophobic core, and the chemotherapeutic drug can be adjusted according to needs and is suitable for broad-spectrum tumor treatment. The drug-loaded silica plastid can generate part of carbon monoxide in a tumor high-concentration hydrogen peroxide (H2O2) environment and release internally-loaded chemotherapeutic drugs. Under the action of ultrasound (US), the multifunctional silicon plastid can realize fixed-point release of chemotherapeutic drugs DOX and carbon monoxide at a tumor site, the enrichment and uptake of the drugs at the tumor site are greatly improved, in addition, the system is combined with the alphaPD-L1 antibody, the immunosuppressive PD-L1 / PD-1 axis can be blocked, T cells are recruited to attack tumors, meanwhile, the immunosuppressive regulatory T cells (Tregs) are reduced, and the tumor treatment effect is improved. The tumor inhibition can be enhanced; the pulmonary metastasis can be obviously reduced.

The present invention belongs to the technical field of radiopharmaceutical chemistry and nuclear medicine diagnosis and treatment and relates to a radiolabeled FAPI complex, a preparation method therefor, and a use thereof. The general structural formula of FAPI capable of realizing radionuclide labeling is as shown below: wherein R is a nitroimidazole group or -COOH; X is a chelating group or a chelating structure chelated with a radionuclide; L1 and L2 are linking groups; and A is an adjusting atom of an FAP-targeting group, and all the A atoms are H atoms or F atoms. The synthesis method for a radionuclide-labeled precursor of the present invention is simple and suitable for various nuclide labels, the labeling method is convenient, and the label has high radiochemical purity and good stability. The radiolabeled FAPI complex shows high affinity and specificity for FAP in a cell experiment and a high tumor uptake and target to non-target ratio in a tumor-bearing mouse, and is a potential FAP-targeting radioactive diagnosis and treatment drug.

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.

The application provides a recombinant fusion protein containing 1) an anti-PD-L1 antibody or an antigen-binding fragment thereof, and 2) an VEGF binding peptide, wherein the N-terminus of the heavy chain or the light chain of the anti-PD-L1 antibody or the antigen-binding fragment thereof is linked, via a linker, to the VEGF binding peptide. Also provided is a nucleic acid molecule for encoding the recombinant fusion protein, an expression vector containing the nucleic acid molecule, a method for preparing the recombinant fusion protein, and a method for treating a disease associated with PD-L1 and / or VEGF signaling using the recombinant fusion protein.

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 herein are anti-Programmed Death-Ligand (PD-L1) antibodies, antigen-binding fragments thereof, multispecific antibodies and encoding polynucleotides. Also provided are PD-L1-targeted phthalocyanine dye conjugates, compositions and articles of manufacture containing the conjugates, and methods for their administration to subjects for photoimmunotherapy. In some embodiments, the anti-PD-L1 antibodies, fragments, and conjugates specifically bind to human PD-L1. Among the anti-PD-L1 antibodies are human antibodies and humanized antibodies. Also provided are methods and uses employing the provided anti-PD-L1 antibodies, antigen-binding fragments, and conjugates such for treatment of human patients.

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.

The present invention relates to the use of a PD-L1 binding molecule in improving the stability of a protein-drug conjugate formulation. The present invention also relates to a pharmaceutical composition consisting of the PD-L1 binding molecule and the protein-drug conjugate, and discloses an anti-tumor use thereof.

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.

Antibodies and antigen-binding fragments thereof that immunospecifically bind to PD-1, such as human or mouse PD-1, and are agonists of PD-1 and can induce or promote an immune response that activates immune cell proliferation or activity. Unlike the majority of known anti-PD-1 and anti-PD-L1 antibodies, which reduce the suppression of PD-1 function by e.g., PD-L1 by physically blocking the interaction between PD-1 and an inactivating ligand, although not to be bound by theory, the disclosed antibodies and antigen-binding fragments thereof are currently best understood to immunospecifically bind to an epitope of PD-1 whereby PD-1 is activated directly. Methods for the treatment of cancer comprising administration of the antibodies or antigen-binding fragments to a subject in need thereof. Polynucleotides encoding the antibodies or antigen-binding fragments. Host cells comprising the polynucleotides.

The present disclosure provides bispecific antibodies useful in gene therapy. Specifically, the invention provides a bispecific antibody, and the bispecific antibody comprises a heavy chain variable region (VHVEGF) and a light chain variable region (VLVEGF) which are targeted to a vascular endothelial growth factor (VEGF), and a heavy chain variable region (VHPD-L1) and a light chain variable region (VLPD-L1) which are targeted to a programmed death receptor-ligand 1 (PD-L1). The bispecific antibody provided by the disclosure can be used for gene therapy, such as AAV or mRNA mediated gene therapy, and can effectively block PD-1 / PD-L1 and VEGF / VEGFR pathways, and inhibit tumors in vitro and in vivo.

Disclosed herein is Differential Subclone Eradication and Resistance Analysis (DSER), a method developed to identify molecular targets for improved therapy by direct comparison of genomic features of eradicated and resistant subclones in pre-and post-treatment samples from a patient with BRCA2-deficient metastatic prostate cancer. FANCI and EYA4 were identified as candidate DNA repair-related targets for converting subclones from resistant to eradicable, and RNAi-mediated depletion of FANCI confirmed it as a potential target. The EYA4 alteration was associated with adjacent L1 transposon insertion during cancer evolution upon treatment. L1 activation was inhibited by the antiretroviral drug azidothymidine. In conclusion DSER provides an informative intermediate step toward effective precision cancer medicine, especially in cases with dramatic but temporary metastatic tumor regression. L1 transposon activation may be a modifiable source of cancer genomic heterogeneity, suggesting the potential of leveraging newly discovered triggers and blockers of L1 activity to overcome therapy resistance.

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.