412 results about "CD47" patented technology

The invention provides a nano photosensitizer modified by outer membrane vesicles of genetically engineered bacteria as well as a preparation method and application of the nano photosensitizer. The nano photosensitizer is a nano material with the particle size of 80-120 nm, and the nano photosensitizer modified by the genetically engineered bacterium outer membrane vesicle comprises dipalmitic acid phosphatidylcholine (DPPC), distearoyl phosphatidylcholine (DSPC), dioleoyl lecithin (DOPC), cholesterol, a small molecule dye and CD47nb-OMV membrane protein. The chemical structure of the small molecule dye is shown as a formula I or a formula II. The nano photosensitizer OBDlp modified by outer membrane vesicles of genetically engineered bacteria serves as a novel nano photosensitizer, tumor targeting PTT is mediated through NIR II FL / PA imaging, tumor immunogenicity is improved, antigen presenting cells are activated, and infiltration and functionalization of CD8 + T cells are caused. And OBDlp and laser are combined to induce release of a large amount of DAMPs and trigger ICD to promote maturation of cDC1s. Meanwhile, a CD47 nano antibody carried by the nano photosensitizer induces polarization of M1 phenotype macrophages by blocking a CD47-SIRP alpha signal transduction axis, and an immunosuppression tumor microenvironment is reversed.

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 present invention discloses a nano antibody against BCMA and its preparation method and application, and relates to the field of biomedical technology. The present invention uses CRISPR / Cas9 technology to knock out B2M and TRAC genes in T cells to prepare universal CAR-T cells; the nano antibody targeting BCMA and the natural ligand SIRPα extracellular N-terminal V region of CD47, the transmembrane region of CD28, the intracellular signal region of 4-1BB and the intracellular signal region of CD3ζ are connected in series to form a dual-targeted chimeric antigen receptor for the treatment of multiple myeloma, so as to solve the high recurrence problem faced by CAR-T cell therapy in the treatment of multiple myeloma. The universal CAR-T cells prepared by the present invention have strong killing activity against multiple myeloma cells, effectively improve the treatment effect, and provide a key material for the subsequent development of adoptive immunotherapy with high efficiency and lasting anti-tumor activity.

The present invention provides an anti-human CD47 antibody or an antigen-binding fragment thereof, a preparation method and use. The present invention also provides an isolated polynucleotide encoding the antibody or antigen-binding fragment thereof and a vector comprising the isolated polynucleotide of the present invention. The present invention also provides the use of the antibody or antigen-binding fragment of the present invention in the preparation of a medicament for treating and / or preventing a disease that benefits from enhancing an immune response, wherein the disease is cancer.

The present invention provides cells (Immune Checkpoint Junction 'ICE' cells) having enhanced Immune Checkpoint Junction function. In some embodiments, the ICE cells have a PD-1 conjugation function (PD-1 conjugant cells). The ICE cells reduce adaptability and innate immunity when transplanted into a subject as compared to parental cells with corresponding unmodified immune checkpoint conjugation function. In some embodiments, the PD-1 zygote cells are low immune pluripotent (HIP) cells. In further embodiments, the HIP cell is type O blood (HIPO), rhesus monkey factor (Rh) negative (HIP-), or both type O and type Rh (HIPO-). In other embodiments, the PD-1 zygote cells have been derived or differentiated from HIP, HIP-, or HIPO-cells. In other embodiments, the ICE cell expresses a ligand that binds to a suppressive immune cell receptor selected from the group consisting of a LILRB1 zygote, a LILRB3 zygote, and a TIM3 zygote. In other embodiments, the ICE cell is a PD-1 zygote cell that also expresses a ligand that binds to another inhibitory immune cell receptor selected from the group consisting of CD47, truncated CD47, a LILRB1 zygote, a LILRB3 zygote, and a TIM3 zygote.

The invention discloses a magnetic bead for eliminating an anti-CD47 monoclonal antibody drug, a preparation method of a reagent and a detection method, the immunomagnetic bead comprises a carboxyl magnetic bead located in the immunomagnetic bead and a human CD47 recombinant protein wrapping the periphery of the carboxyl magnetic bead, and the particle size of the immunomagnetic bead is 100 nanometers; according to the method, only one round of adsorption is needed, the serum magnetic bead mixed solution can be placed on the magnetic frame for magnetic separation after full vortex mixing, interference can be completely removed, the time is very short, and detection can be completed within 1 min.

The present invention belongs to the field of biotechnology, and specifically relates to an antibody targeting CD47 and its application. The anti-human CD47 antibody provided by the present invention can effectively bind to recombinant CD47 protein, block the binding of CD47 to its biological ligand SIRPa, and effectively identify and bind to CD47 positive tumor cells. At the same time, the CD47 antibody does not cause significant hemagglutination reaction and red blood cell binding of human red blood cells at high concentrations.

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 present invention provides anti-SIRPα antibodies and antigen-binding fragments thereof, which can effectively block the binding of SIRPα and CD47, thereby effectively promoting the phagocytosis of tumor cells by macrophages, effectively inhibiting the growth of tumors, and have good drug development prospects.

High affinity SIRP-α reagent are provided, which (i) comprise at least one amino acid change relative to the wild-type protein; and (ii) have an increased affinity for CD47 relative to the wild-type protein. Compositions and methods are provided for modulating phagocytosis in a mammal by administering a therapeutic dose of a pharmaceutical composition comprising a high affinity SIRPα reagent, which blocks the physiological binding interaction between SIRPα and its ligand CD47.

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).

Proposed is a composition for preventing or treating lung diseases. The composition may contain CD47-overexpressing mesenchymal stem cells as an active ingredient. CD47-overexpressing mesenchymal stem cells, even when not autologous, show a high survival rate in vivo and the ability to migrate to lung tissue, reduce the inflammatory response in lung tissue, and exhibit a fibrosis-inhibiting effect. CD47-overexpressing mesenchymal stem cells can be widely used for the prevention or treatment of various lung diseases related to inflammation or fibrosis of the lungs.

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 invention relates to a method for preparing cardiac organoids derived from human pluripotent stem cells, and an efficacy and toxicity evaluation technique. When the cardiomyocytes and cardiac organoids purified by a CD47 surface marker, of the present invention, are used, mature cardiomyocytes and cardiac organoids can be formed, and the cardiomyocytes and cardiac organoids are characterized in that mature cardiomyocytes having uniform contractile ability and a large surface area are formed at a high rate, and thus the present invention can be effectively used in cardiovascular disease modeling including that in toxicity evaluation and drug screening.

The invention discloses a stem cell-derived function-enhanced mesenchymal stromal cell as well as a preparation method and application thereof. The preparation method comprises the following steps: inserting an IL-10 gene coding sequence and a CD47 gene coding sequence into a human pluripotent stem cell; a neural crest cell differentiation culture medium containing a Wnt pathway agonist and an ALK5 inhibitor is used for carrying out induced differentiation culture on the CD47 positive human pluripotent stem cells to obtain the neural crest cells. The neural crest cells are subjected to induced differentiation culture by adopting a transition culture medium containing an epidermal growth factor, a fibroblast growth factor 2 and a cell apoptosis inhibitor and a mesenchymal stromal cell differentiation culture medium containing the epidermal growth factor, the fibroblast growth factor 2 and a platelet growth factor in sequence; according to the present invention, with the combination of the specific embodiments, the obtained mesenchymal stromal cell highly expresses CD47 and IL-10, the expression of the CD47 can help the transplanted cell escape from the attack of the immune system and prolong the cell survival time, and the expression of the IL-10 can be used for anti-inflammation.

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.

Disclosed herein are engineered cells and / or hypoimmunogenic cells including engineered and / or hypoimmunogenic stem cells, engineered and / or hypoimmunogenic cells differentiated therefrom, engineered and / or hypoimmunogenic CAR-T cells (primary or differentiated from engineered and / or hypoimmunogenic stem cells) and related methods of their use and generation. Provided herein are engineered and / or hypoimmunogenic cells exhibiting reduced expression of MHC class I and / or MHC class II human leukocyte antigens and T-cell receptors. In some embodiments, such cells also exogenously express one or more tolerogenic factors such as CD47 and one or more chimeric antigen receptors (CAR)s.

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