288 results about "CD47" patented technology

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.

Provided by the present invention are a bispecific T-cell engager, recombinant oncolytic virus thereof, and use thereof. The present invention provides an αCD47 and αCD3 bispecific T-cell engager. The present invention also provides an isolated nucleic acid molecule that encodes said bispecific T-cell engager. The present invention also provides an expression framework of said bispecific T-cell engager BiTE. The present invention also provides a recombinant oncolytic virus, and said oncolytic virus is operably inserted with or contains the expression framework of said bispecific T-cell engager BiTE. In the present invention, the bispecific T-cell engager is combined with the oncolytic virus, and in comparison with pure gene therapy or virotherapy, the oncolytic virus significantly enhances the inhibition capability on malignant tumors.

The invention discloses a mesenchymal stem cell membrane bionic nano-enzyme for targeted therapy of Parkinson's disease as well as a preparation method and application of the mesenchymal stem cell membrane bionic nano-enzyme. The mesenchymal stem cell membrane bionic nano enzyme comprises an inner core and a mesenchymal stem cell membrane, wherein the inner core is composed of mesoporous polydopamine nanoparticles, and the mesenchymal stem cell membrane coats the inner core. The medicine contains the mesenchymal stem cell membrane bionic nano enzyme. The mesenchymal stem cell membrane bionic nano-enzyme disclosed by the invention shows good biocompatibility, and can be homed to a Parkinson disease region in the brain under the mediation of CXCR4 and VLA-4 specific membrane proteins. In addition, through the CD47 membrane protein expressed on the surface, the removal of the immune system can be avoided, so that the action time in the body is prolonged. The nano-enzyme is helpful for eliminating reactive oxygen free radicals, reducing oxidative stress level and reducing damage of neuroinflammation to dopaminergic neurons, so that safe and efficient treatment of Parkinson's disease is realized.

The invention relates method of treatment of cancer using novel bispecific antibodies carrying a different specificity for each binding site of the immunoglobulin molecule, where one of the binding sites is specific for CD47 and the second is specific for mesothelin (MSLN). In addition, the disclosure contains methods of treatment using novel bispecific antibodies in combination with anti-PD-1 antibody.

The invention discloses a double-target chimeric antigen receptor for co-expression of CD47 and IL-15, a CAR-T cell and application of the CAR-T cell, and belongs to the technical field of genetic engineering, the double-target chimeric antigen receptor comprises a single-chain antibody scFv-EGFRv III, a single-chain antibody scFv-VEGF, CD47 and IL-15; the nucleotide artificial sequence of the single-chain antibody scFv-EGFRv III is as shown in SEQ ID NO. 6; the nucleotide artificial sequence of the single-chain antibody scFv-VEGF is as shown in SEQ ID NO. 9. According to the application disclosed by the invention, by performing sequence optimization on targets EGFRvIII and VEGF, the anti-tumor effect of CAR-T cells in glioblastoma can be improved, and by integrating immune checkpoint molecules CD47 and interleukin-15, the immunosuppression function of a CD47-SIRP alpha signal channel can be locally exerted.

The present invention discloses a CD47-specific molecular imaging probe and its preparation method and application, which relates to the molecular imaging, nuclear medicine and nano-antibody technology fields of tumor diagnosis and treatment, including human CD47-specific monovalent nano-antibody probes and human CD47-specific nano-antibody fusion protein probes; its preparation method comprises: modifying CD47-specific nano-antibody C2 by compounds, synthesizing radionuclide labeling precursors, and preparing the CD47-specific molecular imaging probe by radionuclide labeling; the prepared probe is applied to immune PET imaging and radioimmunotherapy of malignant tumors. The present invention has the advantages of simple preparation process, low cost, high specificity, high stability, and easy clinical transformation. It can realize non-invasive visualization of heterogeneous expression of CD47, screen patients with high expression of CD47, and further carry out CD47-specific radioimmunotherapy, that is, realize integrated diagnosis and treatment.

The invention provides application of a CD47 gene in detection of pig litter size phenotype and application of an SNP site of the CD47 gene in gene expression regulation. It is found that the CD47 gene is regulated and controlled by the SNP site rs323354626, it is further found that the rs323354626 site and the phenotype of the total litter size of sows show the highest significance, and it is indicated that the CD47 gene and the total litter size of the sows have large correlation. In three main commercial varieties of pigs, namely Duroc, Landrace and Yorkshire, the CD47 expression level in testis tissues is negatively correlated with the litter size, which indicates that the expression mode of the CD47 gene may influence the reproductive performance of the pigs, and the litter size phenotype of the pigs can be detected by detecting the CD47 gene expression level in the testis of the breeding pigs or somatic cells of the sows. Or the litter size of the pigs is influenced by regulating and controlling the expression level of the CD47 gene through the rs323354626 site, and the discovery lays a foundation for improving the breeding efficiency of the pigs, especially for a breeding method for increasing the litter size.

The invention relates method of treatment of cancer using novel bispecific antibodies carrying a different specificity for each binding site of the immunoglobulin molecule, where one of the binding sites is specific for CD47 and the second is specific for mesothelin (MSLN). In addition, the disclosure contains methods of treatment using novel bispecific antibodies in combination with anti-PD-1 antibody.

Provided herein are methods of treating a KRAS mutant cancer (e.g., a KRAS G12C mutant cancer or a KRAS G12D mutant cancer) in a subject, comprising administering to the subject an effective amount of an agent that blocks the interaction between CD47 and SIRPα and an effective amount of a KRAS inhibitor (e.g., a KRAS G12C inhibitor wherein the cancer is a KRAS G12C mutant cancer, or a KRAS G12D inhibitor wherein the cancer is a KRAS G12D mutant cancer). Also provided are methods of stimulating phagocytosis of a population of cancer cells that express a KRAS mutant protein (e.g., a KRAS G12C mutant protein or a KRAS G12D mutant protein) by macrophages, comprising contacting the population with an effective amount of a therapeutic agent that blocks the interaction between CD47 and SIRPα and an effective amount of a KRAS inhibitor (e.g., a KRAS G12C inhibitor wherein the KRAS mutant protein is a KRAS G12C mutant protein, or a KRAS G12D inhibitor wherein the KRAS mutant protein is a KRAS G12D mutant protein).

The invention discloses a sequential anti-tumor strategy based on combination of improved tumor microenvironment (TME) and CAR T and application of the sequential anti-tumor strategy, belongs to the technical field of biological medicine, and particularly relates to a sequential anti-tumor strategy based on combination of improved tumor microenvironment (TME) and CAR T. According to the strategy, tumor fibrosis and an acidic microenvironment are improved at the same time by applying a tumor-associated fibroblast (CAF) targeted drug and a proton pump inhibitor, and then sequential injection of CAR T is performed for combined treatment of solid tumors. Wherein the CAF targeting drug is selected from all-trans retinoic acid, calcipotriol, losartan and minetil, the proton pump inhibitor is selected from lansoprazole, omeprazole, pantoprazole, rabeprazole and esomeprazole, and the CAR T receptor or ligand is selected from mesothelin, protein tyrosine kinase 7, NKG2D, CD47, B7-H3, MUC1 and HER2; the sequential administration strategy firstly destroys a compact physical barrier of a tumor microenvironment, improves acidity of a tumor site, ensures infiltration, survival and proliferation of CAR T at the tumor site, and then utilizes specificity of CAR T to inhibit growth of solid tumors in a targeted manner, especially triple negative breast cancer with a high malignancy degree.

The invention relates to a method or application of combination of an anti-TROP2 antibody drug conjugate and an anti-PD-L1 / CD47 bispecific antibody or antigen binding fragment in tumor treatment.

The present disclosure provides multispecific binding agents (e.g., antibodies, such as bispecific antibodies) that have a first binding domain that binds to CD47, including human CD47, and one or more additional binding domains that bind to one or more targets that are not CD47, such as PD-L1 and uses thereof.

Provided is a fusion protein, comprising a first binding domain that specifically binds a tumor-associated antigen, and a second binding domain that specifically binds a CD47 protein, wherein the second binding domain comprises a mutant of a human SIRPα variant 1. Also provided are an immunoconjugate, nucleic acid molecules, vectors, compositions, and cells related to the fusion protein and preparation methods therefor, and the uses thereof in the preparation of medicaments.

Therapeutic compounds for red blood cell-mediated delivery of an active pharmaceutical ingredient to a target cell are described. The therapeutic compounds are configured to bind CD47 on the surface of a red blood cell and to be subsequently transferred to CD47 on the surface of the target cell, the therapeutic compound ultimately being internalized by the target cell via endocytosis. The target cell may be a cancer cell.

The present disclosure generally relates to binding agents capable of targeting tumor cells and / or immune cells and their use to treat cancer. The binding agents of the present disclosure comprise one or more antigen-binding domains of a single-domain antibody capable of binding to cluster of differentiation 36 (CD36), programmed cell death protein 1 (PD-1), and / or cluster of differentiation 47 (CD47). The binding agents of the present disclosure may be monospecific or multispecific and may be in monomeric or multimeric form.

Therapeutic compounds for red blood cell-mediated delivery of an active pharmaceutical ingredient to a target cell are described. The therapeutic compounds are configured to bind CD47 on the surface of a red blood cell and to be subsequently transferred to CD47 on the surface of the target cell, the therapeutic compound ultimately being internalized by the target cell via endocytosis. The target cell may be a cancer cell, a virus-infected cell, or a fibrotic cell.

Methods are provided for targeting cells for depletion, including without limitation tumor cells such as solid tumor cells, in a regimen comprising contacting the tumor and immune effector cells with an effective dose of an anti-MSDC agent that reduces the abundance, immunosuppressive activity, or tumor recruitment of CXCR2+ granulocytic-myeloid derived suppressor cells, for example, an inhibitor of CXCR2; in combination with an effective dose of an inhibitor of CD47 / SIRPα signaling.

The present invention relates to a composition comprising a CD47-SIRPα blocker and one or more anticancer agents: wherein the CD47-SIRPα blocker is represented by a compound of formula (I). The present invention also relates to a method for treating cancer in a subject by administering a therapeutically effective amount of a CD47-SIRPα blocker represented by formula (I) in combination with one or more anticancer agents.

The present invention provides methods of treating ischemic and traumatic central nervous system injury by administering an antagonist of the interaction between CD47 and SIRPa. Also provided are method of increasing efferocytosis after a traumatic or ischemic CNS injury by administering an antagonist of the interaction between CD47 and SIRPa.

To provide a high affinity SIRP-α D1 domain or variant thereof that binds CD47 with higher affinity than wild-type SIRP-α (signal-regulatory protein α), which is useful to target a cell (e.g., a cancer cell or a cell of the immune system), to increase phagocytosis of the target cell, to eliminate immune cells such as regulatory T cells, to kill cancer cells, to treat a disease (e.g., cancer) in a subject, or any combinations thereof.SOLUTION: The present invention provides a polypeptide, comprising: a SIRP-α D1 variant comprising a SIRP-α D1 domain, or a fragment thereof, having an amino acid mutation at residue 80 relative to a wild-type SIRP-α D1 domain; and at least one additional amino acid mutation relative to a wild-type SIRP-α D1 domain at a residue selected from the group consisting of: residue 6, residue 27, residue 31, residue 47, residue 53, residue 54, residue 56, residue 66, and residue 92.SELECTED DRAWING: Figure 3

Disclosed herein are monospecific and multispecific single chain antibodies having specificity for one or more of CD47, PD-L1, HSA, CD33, LAG3, and CD16.

This disclosure provides anti-CD47 antibodies or antigen-binding portions thereof comprising a modified Fc region that activates FcγRs and enhances in vivo antitumor activity. This disclosure further provides a humanized CD47 / SIRPα / FcγR mouse model for evaluating anti-CD47 antibodies or antigen-binding portions thereof.

The present disclosure generally relates to binding agents that are capable of targeting tumor cells and immune cells. The binding agents of the present disclosure are multispecific and comprise antigen binding domains that are capable of binding to Dopamine Receptor D2 (DR2), to Programmed Cell Death Protein 1 (PD-1) and / or to Cluster of Differentiation 47 (CD47). The multispecific binding agents of the present disclosure may be used to treat subjects in need thereof.

Provided is an antibody capable of specifically binding to CD38, or an antigen-binding portion thereof. Also provided is a recombinant fusion protein, comprising: i) a CD38 antibody or an antigen-binding portion thereof; and ii) a CD47 binding peptide, wherein the CD47 binding peptide is linked to an N-terminus of a heavy chain or light chain of the CD38 antibody or the antigen-binding portion thereof, and the CD47 binding peptide is an extracellular Ig-like domain of a signal regulatory protein (SIRP).

The present application provides a monoclonal antibody targeting human carcinoembryonic antigen CEACAM5 / 6, and a bispecific antibody capable of simultaneously targeting human carcinoembryonic antigen CEACAM5 / 6 and human CD47, a preparation method and applications. Specifically, it relates to an anti-human CD47 antibody and antigen-binding fragments thereof capable of simultaneously (1) specifically binding to human CD47 protein and blocking its binding to SIRPalpha, thereby thus blocking the inhibitory effect of CD47 on SIRPalpha-expressing macrophages; (2) specifically binding to human carcinoembryonic protein CEACAM5 / 6. The present application also relates to a preparation method and uses of the bispecific antibody.

Provided is an antibody capable of specifically binding to CD38, or an antigen-binding portion thereof. Also provided is a recombinant fusion protein, comprising: i) a CD38 antibody or an antigen-binding portion thereof; and ii) a CD47 binding peptide, wherein the CD47 binding peptide is linked to an N-terminus of a heavy chain or light chain of the CD38 antibody or the antigen-binding portion thereof, and the CD47 binding peptide is an extracellular Ig-like domain of a signal regulatory protein (SIRP).

Antibodies are provided which comprise at least one Fab portion that binds CD47 and at least one Fab portion that binds the tumor associated antigen (TAA) CD20; wherein the Fab portion that binds CD47 exhibits low affinity for CD47; and, wherein the Fab portion that binds CD20 exhibits high affinity for CD20; and, wherein the antibody selectively binds CD47 and blocks CD47 interaction with SIRPα in tumor cells while exhibiting no substantial binding to CD47 in normal cells.

The invention discloses an antigen binding polypeptide combined with CD47 or an antigen binding part and application thereof. Specifically, the invention provides an antigen binding polypeptide binding CD47 and an antigen binding part thereof, nucleic acid encoding the antigen binding polypeptide and the antigen binding part, a carrier containing the nucleic acid, a cell containing the carrier, a pharmaceutical composition containing the antigen binding polypeptide and the antigen binding part, and application of the antigen binding polypeptide and the antigen binding part in reducing tumors or inhibiting growth of tumor cells, treating cancers, promoting phagocytosis of macrophages and the like.

The present disclosure relates to antibodies and antibody derivatives that bind to CD47 (also known as IAP, MER6 and OA3) and methods of using the same. In certain embodiments, an anti-CD47 antibody or antibody derivative disclosed herein exhibits reduced binding to a red blood cell.

The invention discloses a coupling molecule with an effect of promoting macrophages to selectively swallow extracellular goods as well as a preparation method and application of the coupling molecule, and belongs to the technical field of biological medicines. The coupling molecule disclosed by the invention is a double-targeting polypeptide and consists of a macrophage targeting peptide fragment, a linker and a target cell targeting peptide fragment, wherein the target cell targeting peptide fragment comprises peptide fragments targeting tumor cells and apoptotic cells. One end of the dual-targeting polypeptide is connected with macrophages, the other end of the dual-targeting polypeptide is connected with tumor cells / apoptotic cells, and the interaction between the macrophages and the tumor cells / apoptotic cells is improved in a molecular glue mode. Aiming at tumor cells, the dual-targeting polypeptide can enhance the phagocytosis and killing effects of macrophages on the tumor cells under the action of a CD47 antibody, so that the anti-tumor effect is achieved; aiming at apoptotic cells, the dual-targeting polypeptide can promote the interplant effect of macrophages, so that the anti-inflammatory effect is achieved. Therefore, the dual-targeting polypeptide disclosed by the invention has relatively good drug development potential.