1505 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.

The invention provides an anti-human CD117 monoclonal antibody and an application thereof. The anti-human CD117 monoclonal antibody comprises three heavy chain complementary determining regions CDR-H1, CDR-H2 and CDR-H3 and three light chain complementary determining regions CDR-L1, CDR-L2 and CDR-L3, the amino acid sequence of the CDR-H1 is as shown in SEQ ID NO: 1, the amino acid sequence of the CDR-H2 is as shown in SEQ ID NO: 2, the amino acid sequence of the CDR-H3 is as shown in SEQ ID NO: 3, the amino acid sequence of the CDR-L1 is as shown in SEQ ID NO: 4, the amino acid sequence of the CDR-L2 is as shown in SEQ ID NO: 5, and the amino acid sequence of the light chain complementary determining regions is as shown in SEQ ID NO: 6. The amino acid sequence of the CDR-L3 is as shown in SEQ ID NO: 6. Compared with the existing known anti-human CD117 monoclonal antibody, the antibody disclosed by the invention shows better cellular level biology, and is expected to show a good clinical effect in the aspect of preventing and treating related diseases.

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.

The present disclosure is directed to compounds of Formula (I):which modulate PD-1 / PD-L1 protein / protein interaction, compositions, and methods of treating various diseases, including infectious diseases and cancer.

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 invention provides a radionuclide-labeled PDL1 targeting small protein as well as a preparation method and application thereof. Specifically, the invention provides a radionuclide-labeled PD-L1 targeted small protein probe and a preparation method thereof, and the radionuclide-labeled PD-L1 targeted small protein probe is used for diagnosis of malignant tumors, accurate positioning of focuses, curative effect monitoring and radioimmunotherapy. The small protein conjugate provided by the invention can be prepared by labeling in a temperature range from room temperature to 60 DEG C, and compared with other nuclides or linkers, the coupling efficiency is higher, and the finished product is more stable.

Herein is reported an anti-TREM2 / Abeta protein antibody comprising a first binding site binding to human TREM2 comprising a heavy chain variable domain comprising a HVR-H1 of SEQ ID NO: 305, a HVR-H2 of SEQ ID NO: 306 and a HVR-H3 of SEQ ID NO: 307, and a light chain variable domain comprising a HVR-L1 of SEQ ID NO: 309, a HVR-L2 of SEQ ID NO: 310 and a HVR-L3 of SEQ ID NO: 311 (TREM2 3295), or a heavy chain variable domain comprising a HVR-H1 of SEQ ID NO: 329, a HVR-H2 of SEQ ID NO: 330 and a HVR-H3 of SEQ ID NO: 331, and a light chain variable domain comprising a HVR-L1 of SEQ ID NO: 333, a HVR-L2 of SEQ ID NO: 334 and a HVR-L3 of SEQ ID NO: 335 (TREM2 3306), and a second binding site binding to human Abeta protein comprising a heavy chain variable domain comprising a HVR-H1 of SEQ ID NO: 09, a HVR-H2 of SEQ ID NO: 10 and a HVR-H3 of SEQ ID NO: 11, and in the light chain variable domain a HVR- L1 of SEQ ID NO: 13, a HVR-L2 of SEQ ID NO: 14 and a HVR-L3 of SEQ ID NO: 15 (Abeta 8675).

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 present invention the invention concerns bifunctional compounds of Formula (I) A-T-L1-AG, Formula (II) A-L1-Con(L2-AG)n or Formula (III) Ak´-Th-L3 ii-AGj' wherein A is a protein that binds to the hinge region of galactose deficient IgA1 antibodies or a protein that binds to autoantibodies of galactose deficient IgA antibodies and AG is an asiaglycoprotein receptor binding moiety (ASGPR binding moiety). L1, Con and L2 are part of a linker between A and AG. The A has the ability to bind to antibodies that are a cause of IgA nephropathy and the asiaglycoprotein receptor binding moiety binds to hepatic cells thereby initiating endocytosis and removal of the antibodies that are a cause of IgA nephropathy from the blood stream.

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.

A photosensitizer chimera targeting PD-L1 protein, and a preparation method therefor and a use thereof. The photosensitizer chimera is of an X-R-G structure, wherein X is a photosensitizer unit, R is a linker, G is a polypeptide unit targeting PD-L1 protein, the photosensitizer is a porphyrin photosensitizer, and the excitation light wavelength of the photosensitizer is longer than 550 nm; the molar absorption coefficient at the maximum absorption wavelength longer than the wavelength of 550 nm is greater than 1000 M -1cm-1; the quantum yield of a triplet state exceeds 0.01; the linker is selected from the following structural formulas, wherein the amino side of the linker is connected to the photosensitizer unit, the carboxyl side of the linker is connected to the polypeptide unit, and n is an integer of 0-50; the binding constant of the polypeptide and h-PD-L1 is less than 20 µm. Combination therapy of immune checkpoint blockade and cytotoxicity induced by the photosensitive chimera based on photodegradation of PD-L1 protein in PD-1 / PD-L1 can cause stronger immune response than monotherapy, and thus the photosensitive chimera has great potential in enhancing antitumor therapy.

Bispecific molecules comprising a 4-1BB binding protein and a PD-L1 binding protein are provided herein. Related monospecific molecules binding to either 4-1BB or PD-L1 are also provided herein. Methods of treatment comprising administering a pharmaceutical composition comprising a bispecific or monospecific molecule as described herein are further provided.

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 relates to an anti-PD-1 single-domain antibody and application thereof. The complementarity determining region of the VHH chain of the anti-PD-1 single-domain antibody comprises a CDR1 with an amino acid sequence as shown in SEQ ID NO.1, a CDR2 with an amino acid sequence as shown in SEQ ID NO.2 and a CDR3 with an amino acid sequence as shown in SEQ ID NO.3. The invention further discloses a preparation method of the anti-PD-1 single-domain antibody. The PD-1 protein is used for immunizing alpaca, an antibody display library is constructed, an antibody combined with the PD-1 protein is screened, the single-domain antibody with high specificity and affinity is obtained, and the single-domain antibody has the capacity of blocking combination of PD-1 and PD-L1 and the function of enhancing immune cells.

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 invention relates to an anti-human PD-1 shark nano antibody and application thereof, and belongs to the technical field of biology. The anti-human PD-1 shark nano antibody provided by the invention is only composed of a heavy chain, the heavy chain comprises a heavy chain variable region, and the antibody heavy chain variable region vNAR comprises CDR1 and CDR3; cDR1 is amino acid residues 25-32 in the amino acid sequence as shown in SEQ ID NO: 2; cDR3 is amino acid residues 84-102 in the amino acid sequence as shown in SEQ ID NO: 2. The invention also provides a coding nucleic acid, an expression vector, a host cell and the like of the anti-human PD-1 shark nano antibody, and also provides a production method and application of the nano antibody. The nano antibody has the advantages of high affinity, high specificity and the like, can effectively block a PD-1 / PD-L1 pathway, and has the potential of being applied to the field of tumor treatment and diagnosis.

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 invention discloses CD44-mediated self-assembled nanoparticles as well as a preparation method and application thereof, and belongs to the technical field of biology. The CD44-mediated self-assembled nanoparticles are formed by self-assembling polylysine with a phenylboronic acid side chain and dopamine-modified hyaluronic acid through electrostatic interaction, and the side-chain phenylboronic acid of the polylysine is connected with the side-chain dopamine on the hyaluronic acid through a covalent bond. The surface of the nanoparticle is connected with a target protein binding unit through a linker, and the target protein binding unit is used for binding a target protein. The synthesis process is simple, the components are safe, the prepared CD44-mediated self-assembled nano material can efficiently degrade tumor cell extracellular proteins such as PD-L1 and HER2, the specificity is high, the degradation rate is high, and the CD44-mediated self-assembled nano material has a very good application prospect in the field of treatment of diseases such as tumors.

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.