135 results about "CD47" patented technology

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.

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.

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

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.

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 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.

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

Provided is a use of a recombinant fusion protein in the preparation of a drug for treating an autoimmune disease that can benefit from the reduction or elimination of CD20+B cells (for example, CD20+ B cell depletion therapy). The recombinant fusion protein comprises i) a CD47-binding peptide, and ii) an anti-CD20 antibody or an antigen-binding portion thereof, wherein the CD47-binding peptide comprises a first extracellular Ig-like domain (SIRPαD1) of signal regulatory protein α (SIRPα), and the anti-CD20 antibody or the antigen-binding portion thereof comprises a heavy chain variable region, a heavy chain constant region, a light chain variable region, and a light chain constant region. The heavy chain variable region comprises VH-CDR1, VH-CDR2, and VH-CDR3, and the light chain variable region comprises VL-CDR1, VL-CDR2, and VL-CDR3, wherein the VH-CDR1, VH-CDR2, VH-CDR3, VL-CDR1, VL-CDR2, and VL-CDR3 respectively comprise amino acid sequences as shown in GYTFTSYN (SEQ ID NO: 1), IYPGNGDT (SEQ ID NO: 2), ARSTYYGGDWYFNV (SEQ ID NO: 3), SSVSY (SEQ ID NO: 4), ATS, and QQWTSNPPT (SEQ ID NO: 5). The heavy chain constant region has the binding capacity for an FcR or a complement system protein. The CD47-binding peptide is linked to the N-terminus of the heavy chain variable region or light chain variable region of the anti-CD20 antibody or the antigen-binding portion thereof.

An mRNA composition for treating cancer is provided. The mRNA composition for treating cancer includes an mRNA encoding a CD47-targeted chimeric antigen receptor (CAR) and an mRNA encoding interleukin-12 (IL-12).

The present present disclosure relates to a CD47-SIRPα blocking agent of formula (I) stereoisomers thereof, and pharmaceutically acceptable salts, solvates, amides and esters of the compound of formula (I) and stereoisomer thereof for use in a method of treating or delaying progression of a disease or a disorder mediated by CD47-SIRPα pathway in a human subject suffering from said disease, such as cancer.

Disclosed is a SIRPα-targeting antibody or an antigen-binding fragment thereof, comprising a light chain variable region and / or a heavy chain variable region. The antibody or the antigen-binding fragment thereof binds to human SIRPα-V1 and human SIRPα-V2, but weakly or does not bind to human SIRPβ and SIRPγ, does not bind to human T cells, and has the function of blocking the binding of SIRPα to CD47. Further disclosed are a bispecific antibody comprising same, a method for preparing the antibody or the antigen-binding fragment thereof and an application thereof. The unique properties of the disclosed antibody or the antigen-binding fragment thereof enable same to be more suitable for the development of drugs for an antibody or antigen-binding fragment against a human SIRPα target. As a candidate drug, same can be administered alone or in combination, providing a new or even better choice for the combined immunotherapy of tumors.

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.

Disclosed herein are monospecific and multispecific antibodies specific for CD28 and CD3E, and one or more of OX-40, CD40, 4-1BB, HSA, IL-22, PD-L1, CD16, CD47, CD33, LAG3, and EGFR.

The application belongs to the field of antibodies, and particularly relates to a CD47-targeting antibody mutant and application thereof, wherein the amino acid sequence of the heavy chain variable region of the CD47-targeting antibody mutant is shown as SEQ ID NO: 3, and the amino acid sequence of the light chain variable region of the CD47-targeting antibody mutant is shown as SEQ ID NO: 4; the application implements multidimensional developability optimization on the light and heavy chain variable regions of the anti-human CD47 antibody through computer-aided molecular design combined with experimental verification, and comprehensively considers parameters such as folding free energy, surface charge distribution, hydrophobic exposure area and local stability, and an optimized mutant is screened; the optimized mutant obtained by the application realizes isoelectric point reduction, hydrophobicity weakening and charge symmetry and hydrophilic exposure improvement under the premise of not reducing affinity, can be used for preparing a drug for treating tumors related to high expression of CD47, and provides a general technical approach for AI-based antibody developability and stability modification.

Provided are compositions and methods for treating Lewis Y antigen positive cancers in mammalian subjects by administering an effective amount of a radionuclide-labeled Lewis Y antigen targeting agent such as an antibody labeled with an alpha particle-emitting radionuclide such as 225Ac. The methods may further include administration of additional agents, such as radiosensitizing agents, immune checkpoint therapies, CD47 blockades, and / or DNA damage response inhibitors.

Novel bispecific heterodimeric immunoglobulins that target both a component of the human CD47 antigen and human CD38 antigen are provided and in particular those comprising an anti-CD38 heavy chain variable region and a light chain variable region and an anti-CD47 heavy chain variable region and a light chain variable region. The present invention also relates to the use of this 5 novel class of bispecific heterodimeric immunoglobulins to treat autoimmune and proliferative diseases and in particular cancers such as hematologic malignancies and solid tumors.

This invention relates to the field of biomedical technology, and more particularly to a CD47-targeting degradation polypeptide compound and its applications. The CD47-targeting degradation polypeptide compound provided by this invention can specifically bind to the CD47 protein on the surface of tumor cells and induce its direct degradation. The polypeptide compound of this invention can target and degrade the CD47 protein on the surface of tumor cells, exhibiting excellent anti-tumor effects without significant toxic side effects, avoiding drawbacks such as blood toxicity, anemia, and thrombocytopenia. It has good biocompatibility and has significant development and application value in the preparation of anti-tumor drugs, and can be used to develop anti-tumor polypeptide drugs.

This disclosure relates to protein complexes targeting CD47, PD-L1, and / or TGFβ, and methods of use thereof. In one aspect, the protein complexes include one or more CD47-binding domains, each including all or a portion of the SIRPα extracellular region; one or more PD-L1-binding domains, each including all or a portion of the PD-1 extracellular region; and optionally one or more TGFβ-binding domains, each including all or a portion of the TGFBR2 extracellular region.

Disclosed herein are dual-specific antibodies that target both human CTLA4 and CD47. Also provided herein are polynucleotides encoding the dual-specific antibodies, pharmaceutical compositions comprising the dual-specific antibodies, and methods of producing the dual-specific antibodies. Also disclosed are medical uses of the dual-specific antibodies described herein in the treatment of cancer.

The invention belongs to the technical field of biological medicines, and particularly relates to a drug-loaded vesicle for treating thyroid cancer as well as a preparation method and application of the drug-loaded vesicle. The drug-loaded vesicle comprises a vesicle, wherein a cavity of the vesicle is loaded with radioactive iodine; the membrane surface of the vesicle is modified with: a) a first single-chain antibody fragment capable of specifically binding to thyroglobulin; according to the present invention, after the intravenous injection, the drug-loaded vesicle can be enriched in the thyroid cancer lesion area of the RAIR-DTC patient, such that the cancer cell proliferation is inhibited while the radioactive iodine is continuously released so as to provide the long-term treatment effect;

The invention relates to the technical field of medicine and biology, and particularly discloses a stress-inducible virus and application thereof.The stress-inducible virus comprises a stress-inducible adenovirus or a stress-inducible lentivirus, the nucleotide sequence of the stress-inducible adenovirus or the stress-inducible lentivirus is shown as SEQ ID NO: 1, and the nucleotide sequence of the stress-inducible adenovirus or the stress-inducible lentivirus is shown as SEQ ID NO: 2. The preparation method comprises the following steps: constructing a virus vector, wherein the virus vector has a nucleotide sequence as shown in SEQ ID NO: 1; and virus packaging: transfecting HEK293T cells by adopting shuttle plasmids containing SEQ ID NO: 1 and skeleton plasmids containing viral genome sequences, and collecting a virus stock solution to obtain the stress induced virus. The invention also discloses application of the stress-induced virus in preparation of medicines for preventing and treating oral tumors. Controllable release of the foreign protein under a specific signal is realized. The therapeutic protein produced by the invention can maximize the curative effect of drugs such as CD47 targeted protein and the like, and meanwhile, the toxic and side effects of the drugs on other tissues of the whole body are reduced.

Provided are protein complexes targeting CD47, PD-L1, and / or TGFβ, and methods of use thereof. In one aspect, the protein complexes include a CD47-binding domain having all or a portion of the SIRPα extracellular region; a PD-L1-binding domain having a VHH that binds to PD-L1; and optionally a TGFβ-binding domain having all or a portion of the TGFBRII extracellular region.

Anti-CD47 / anti-TIGIT bispecific antibody, a preparation method thereof and application thereof. The bispecific antibody comprises: (a) a first antigen binding part, comprising heavy chain variable region (VH) and light chain variable region (VL), VH and VL forming an antigen binding site that specifically binds to CD47; and (b) a second antigen binding part, comprising a single domain antibody (sdAb) that specifically binds to TIGIT, wherein the first antigen binding part and the second antigen binding part are fused with each other. The bispecific antibody can block two modes of tumor immune escape at the same time, thus having a good effect in tumor immunotherapy.

Humanized or chimeric anti-CD47 monoclonal antibodies are provided. The antibodies bind to and neutralize human CD47, and find use in various therapeutic methods. Non-activating antibodies are preferred. Embodiments of the invention include isolated antibodies and derivatives and fragments thereof, pharmaceutical compositions comprising one or more of the humanized or chimeric anti-CD47 monoclonal antibodies; and cell lines which produce these monoclonal antibodies. Amino acid sequences of the antibodies are also provided.

The present invention relates to engineered SIRP alpha variants and methods of use thereof. Signal regulatory protein a (SIRPa) is a regulatory membrane glycoprotein of the SIRP family. The protein is mainly expressed by bone marrow cells and also expressed by stem cells or neurons. SIRPa is used as an inhibitory receptor and interacts with a widely expressed transmembrane protein CD47. The present disclosure relates to engineered SIRPa variants and methods of use thereof.

The application discloses a sequential anti-tumor strategy based on improvement of tumor microenvironment (TME) combined with CAR T and application thereof, and belongs to the technical field of biological medicine, which simultaneously improves tumor fibrosis and acid microenvironment by applying tumor-related fibroblast (CAF) targeting drugs and proton pump inhibitors, and sequentially injects CAR T combined therapy for solid tumors, wherein the CAF targeting drugs are selected from tretinoin, calcipotriol, losartan and minnelide, the proton pump inhibitors are 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 first destroys the dense physical barrier of the tumor microenvironment, improves the acidity of the tumor site, ensures the infiltration, survival and proliferation of CAR T at the tumor site, and then targets and inhibits the growth of solid tumors, especially high-malignancy triple-negative breast cancer, by using the specificity of CAR T.