145 results about "CD137" patented technology

An objective of the present disclosure is to provide anti-CD137 antigen-binding molecules which have immunocyte-activating effect, cytotoxic activity, or anti-tumor activity, and meanwhile have reduced effect on non-tumor tissues such as normal tissues and produce less side effects, and methods of using the same.Anti-CD137 antigen-binding molecules which have immunocyte-activating effect, cytotoxic activity, or anti-tumor activity, and meanwhile have reduced effect on non-tumor tissues such as normal tissues and produce less side effects, are provided by discovering and producing CD137 antigen-binding molecules whose binding activity to CD137 depends on various substances (for example, small molecule compounds) in target tissues. Methods of using the same, pharmaceutical formulations, and such are also provided.The present disclosure also provides an antigen-binding molecule whose binding activity to an antigen varies depending on a small molecule compound, a preparation method thereof, and uses thereof.

The invention belongs to the technical field of bioengineering, and particularly relates to an IL-12-CD137 chimeric protein, a function-enhanced engineered NK cell, and preparation and application thereof. The IL-12-CD137 chimeric protein comprises a signal peptide, an IL-12a protein molecule, a CD137 transmembrane structural domain and a CD137 intracellular structural domain, and has an amino acid sequence as shown in SEQ ID NO: 1. According to the function-enhanced engineered NK cell, the IL-12-CD137 chimeric protein sequence is introduced into an original NK cell, the function-enhanced engineered NK cell expressing Chime-IL12-CD137 is obtained, the amplification capacity and killing capacity of the NK cell can be enhanced, and the function-enhanced engineered NK cell is applied to treatment of tumor and virus-infected diseases of companion animals for the first time.

The present disclosure provides compositions and methods for targeting neoantigens, for example, to treat or prevent cancer. The disclosed embodiments include binding proteins, such as T cell receptors, that bind to the neoantigen: HLA complex. The binding protein further comprises a construct comprising a fusion protein of the CD95 extracellular domain and the CD137 intracellular signaling domain (Fas-41BB), and a CDS coreceptor alpha or beta chain. The disclosed binding proteins are highly sensitive to antigens and are capable of inducing activation of host T cells at low concentrations of peptide antigens. In certain embodiments, binding proteins of the present disclosure (i) have no alloreactivity, substantially no alloreactivity, and / or low risk of alloreactivity, to amino acid sequences from human proteomes and / or (ii) to human HLA alleles. Polynucleotides encoding such binding proteins can be introduced into host cells, such as T cells, and the cells can be used in immunotherapy for the treatment of various cancers.

The present invention relates to a heterotandem bicyclic peptide complex which comprises a first peptide ligand, which binds to Nectin-4, conjugated via a linker to two second peptide ligands, which bind to CD137. The invention also relates to the use of said heterotandem bicyclic peptide complex in preventing, suppressing or treating cancer.

The present invention relates to combination therapies employing tumor targeted anti-CEA / CD3 bispecific antibodies and / or agents blocking PD-L1 / PD-1 interaction in combination with 4-1BB (CD137) agonists, in particular 4-1BBL trimer containing antigen binding molecules that also target FAP, the use of these combination therapies for the treatment of cancer and methods of using the combination therapies.

The invention discloses a chimeric antigen receptor simultaneously targeting GPRC5D and CS1 and application thereof, and relates to the technical field of biological medicines. Spatial epitopes of a GPRC5D antigen and a CS1 antigen are taken as target spots, an scfv region of a GPRC5D antibody and an scfv region of a CS1 antibody are connected in series through Linker, and an optimal structure VH1-VL1-VH2-VL2 is obtained through screening, VH1 and VL1 are anti-GPRC5D scfv, and VH2 and VL2 are anti-CS1scfv. The chimeric antigen receptor constructed by connecting the optimal structure VH1-VL1-VH2-VL2 with a transmembrane region of CD8, a CD137 intracellular signal region and a CD3zeta intracellular signal region in series is used for treating the multiple myeloma, so that the problems of low remission rate and high relapse rate of a CAR-T cell therapy in treatment of the multiple myeloma are solved, and the chimeric antigen receptor is still effective for the multiple myeloma with BCMA negative or low BCMA antigen expression and can be used for treating the multiple myeloma. And a new strategy is provided for clinical treatment of multiple myeloma patients with negative BCMA expression or recurrence after BCMA CAR-T treatment.

This invention relates to binding molecules that bind specifically to CD137 and FAP and their use in medicine, pharmaceutical compositions containing the same, and methods of using the same as agents for treatment and / or prevention of cancer.

The invention relates to an oncolytic virus VSV-aPDL1 / aCD137 for expressing a bispecific antibody as well as a construction method and application of the oncolytic virus VSV-aPDL1 / aCD137. The preparation method comprises the following steps: firstly designing aPDL1 / aCD137, then synthesizing an aPDL1 / aCD137 gene in vitro, amplifying the aPDL1 / aCD137 gene, connecting the aPDL1 / aCD137 gene to a pT7-VSV whole genome plasmid to obtain a virus whole genome plasmid pT7-VSV-aPDL1 / aCD137, and then co-transfecting the plasmid and a helper plasmid to a 293T cell to obtain the VSV-aPDL1 / aCD137 oncolytic virus. According to the present invention, the local anti-tumor immune response of the tumor is activated through the virus, the infiltration of the lymphocyte to the tumor tissue is recruited, the anti-PD-L1 / anti-CD137 bispecific antibody is expressed, the inhibition of the PD-1 / PD-L1 pathway on the T cell is blocked, and the inhibition signal of the PD-1 / PD-L1 pathway on the tumor cell surface is reversed into the CD137 signal of the activated T cell, such that the functional failure of the T cell caused by the PD-1 / PD-L1 pathway can be blocked, and the anti-tumor immune response of the tumor can be inhibited; the function and viability of T cells can be further improved, long-term immune surveillance on tumors is realized, and long-acting anti-tumor immune response is generated. Experiments show that the oncolytic virus can significantly prolong the lifetime of tumor-bearing mice, and a new strategy is provided for development of solid tumor drugs.

The present disclosure provides isolated binding molecules that bind to and activates CD137, vectors comprising a nucleic acid molecules encoding an amino acid sequence of the binding molecules, host cells containing the vectors, methods of making the binding molecules, pharmaceutical compositions containing the binding molecules, and methods of using such antibodies, antibody fragments and derivatives and polypeptides, including methods of treating a disease requiring stimulation of immune responses including cancer.

Provided herein are antibodies or antigen binding fragments thereof having a binding specificity for p95HER2 or for CD73, bispecific antibodies comprising a first antigen binding region that binds to p95HER2 or CD73 and a second antigen binding region that binds to an immune checkpoint molecule or an immune stimulatory molecule, and antibody-drug conjugates thereof. Also provided herein are pharmaceutical compositions comprising the antibodies, antigen binding fragments thereof, bispecific antibodies or antibody drug conjugates thereof, and methods of use thereof. The methods of use include method of treating cancer.

The present invention relates to: an affibody binding specifically to the extracellular domain of CD137; a protein complex comprising the described affibody and an antibody that binds specifically to a protein on the surface of cancer cells or an antigen-binding fragment thereof; and a pharmaceutical composition for preventing or treating cancer, comprising same as an active ingredient. By using the affibody binding specifically to CD137, a protein complex binding specifically to T cells and, simultaneously, binding specifically to an antigen on the surface of various types of cancer cells can be developed and effectively used in the prevention or treatment of blood cancer and solid cancer.

The present application belongs to the field of cell therapy and immunotherapy, and provides a genetically engineered human trophoblast, a preparation method and application thereof. The human trophoblast takes K562 cells as starting cells, and stably expresses membrane-bound interleukin 21, CD137 ligand and Delta-like ligand 1 after genetic engineering. The constructed K562 three-factor trophoblast can significantly improve the expansion efficiency, activation state and functional stability of NK cells and γδT cells. The synergistic mechanism includes enhancing the proliferation, cytotoxicity and stemness maintenance of NK cells and γδT cells through STAT3, NF-κB and Notch signaling pathways, respectively. The human trophoblast has the advantages of good expression stability, significant functional enhancement, and high activity after freezing and recovery.

Provided are trispecific T Cell Engagers or TSMAb's, antibodies that can simultaneously engage three different types of epitopes on the same target or on different targets. More specifically, the invention is directed to trispecific molecules that bind to DLL3, MUC17 or CLDN18.2 and activate CD (cluster of differentiation) molecules (e.g. CD3, CD28 and CD137). Also provided are methods of treating an ailment such as cancer using an antibody (or fragment) against DLL3, MUC17 or CLD18 paired with an antibody (or fragment) of an agonist antibody that activates CD3, CD28 and / or CD137.

The present disclosure relates to combinations of antibodies, or antigen-binding fragments thereof, that bind to CD137, and PD-1 antagonists. The disclosure also relates to methods for treating or ameliorating one or more symptoms of a disease, such as cancer, by administering the combination.

The invention belongs to the technical field of biomedicine and antibody engineering, and relates to a monoclonal antibody capable of being combined with human CD137 protein or a functional fragment of the monoclonal antibody, and application of the monoclonal antibody capable of being combined with the human CD137 protein or the functional fragment of the monoclonal antibody as an antibody conjugate, a chimeric antigen receptor and / or a composition. The monoclonal antibody is specifically combined with cell membrane surface CD137 protein and soluble CD137 protein through a specific nucleic acid sequence and an encoding antibody of the monoclonal antibody, has clear basic characteristics of CD137 combination specificity, sensitivity, affinity and the like, and can be used for detecting cell membrane surface CD137 and body fluid sCD137. The monoclonal antibody capable of being combined with the human CD137 protein, which is obtained by screening, has high sensitivity, high specificity and high affinity.

The name of the invention is T cell activation antibodies. The present invention provides antibodies comprising an antigen binding region that binds to CD137. The present invention also provides a bispecific antibody comprising a first antigen binding region that binds to CD137 and a second antigen binding region that binds to an immune checkpoint molecule, an immune stimulatory molecule or a tumor antigen. The invention provides pharmaceutical compositions comprising the antibodies and methods of treating cancer.

The present invention relates to pharmaceutical formulations of binding agents and their use in pharmaceuticals. In particular, the present invention relates to pharmaceutical formulations of binding agents, such as bispecific antibodies that bind to human PD-L1 and to human CD137. Furthermore, the invention relates to the use of the pharmaceutical formulation according to the invention and to a method for producing a pharmaceutical formulation.

Provided are bispecific T Cell Engagers. More specifically, the invention is directed to bispecific molecules that bind to DLL3, MUC17 or CLD18 and activate CD (cluster of differentiation) molecules (e.g. CD3, CD28 and CD137). Also provided are methods of treating an ailment such as cancer using an antibody (or fragment) against DLL3, MUC17 or CLD18 paired with an antibody (or fragment) of an agonist antibody that activates CD3, CD28 and / or CD137.

The present disclosure relates to chimeric costimulatory receptors (CCR) specific to ICAM-1, e.g., the CCRs that comprise a 4-1BB (CD137) costimulatory domain and a ICAM-1 binding domain (e.g., a ICAM-1 -specific scFv). Composition comprising such CCRs and methods of using such CCRs for preventing and treating a cancer are also provided.

The application discloses a chimeric antigen receptor targeting CEA and a T cell containing the chimeric antigen receptor targeting CEA. The chimeric antigen receptor is composed of a nanobody recognizing a CEA antigen, an extracellular hinge region, a transmembrane region, an intracellular signal region, a self-cleavage polypeptide T2A and a hyaluronidase in sequence. The chimeric antigen receptor can efficiently recognize the CEA antigen, and CD28 and CD137 are used as a costimulatory signal region to activate T cells, thereby playing a cellular immune role, and specifically killing CEA-positive tumor cells, and thus having an important application prospect in the field of tumor cell immunotherapy.

The present disclosure relates to combinations of antibodies, or antigen-binding fragments thereof, that bind to CD137, and PD-1 antagonists. The disclosure also relates to methods for treating or ameliorating one or more symptoms of a disease, such as cancer, by administering the combination.

The present disclosure provides isolated binding molecules that bind to and activate CD137, vectors comprising nucleic acid molecules encoding the amino acid sequence of the binding molecules, host cells containing the vectors, methods of making the binding molecules, pharmaceutical compositions containing the binding molecules, and methods of using such antibodies, antibody fragments and derivatives, and polypeptides, methods of treating diseases requiring stimulation of an immune response, including cancer, are included.

The present application relates to antibody molecules that bind both PD-L1 and CD137 and are able to induce agonism of CD137. The antibody molecules comprise a CDR-based binding site for PD-L1, and a CD137 antigen-binding site that is located in a constant domain of the antibody molecule. The antibody molecules of the invention find application, for example, in the treatment of diseases, such as cancer.

The present invention relates to antibodies (and fragments, variants, fusions and derivatives thereof) with binding specificity for domain 2 of human CD137 which are capable of inhibiting the binding of a reference antibody to human CD137. The antibodies and fragments have utility in the treatment of diseases such as cancer. The invention also relates to pharmaceutical compositions, uses, methods and kits comprising such antibodies.

The present application relates to antibody molecules that bind both PD-L1 and CD137 and are able to induce agonism of CD137. The antibody molecules comprise a CDR-based binding site for PD-L1, and a CD137 antigen-binding site that is located in a constant domain of the antibody molecule. The antibody molecules of the invention find application, for example, in the treatment of diseases, such as cancer.

The present invention relates to a hetero-tandem bicyclic peptide complex, which comprises a first peptide ligand binding to EphA2, wherein the first peptide ligand is conjugated to two second peptide ligands binding to CD137 via a linker. The present invention also relates to the use of the hetero-tandem bicyclic peptide complex in preventing, inhibiting or treating cancer.

Provided are bispecific T Cell Engagers. More specifically, the invention is directed to bispecific molecules that bind to DLL3, MUC17 or CLD18 and activate CD (cluster of differentiation) molecules (e.g. CD3, CD28 and CD137). Also provided are methods of treating an ailment such as cancer using an antibody (or fragment) against DLL3, MUC17 or CLD18 paired with an antibody (or fragment) of an agonist antibody that activates CD3, CD28 and / or CD137.

The problem to be solved by the present invention is to provide more and better options for treating any solid tumor with high frequency microsatellite instability (high frequency MSI or MSI-H) alterations, cervical cancer, endometrial cancer, lung cancer, brain cancer and breast cancer.SOLUTION: The present invention relates to multispecific antibodies comprising an antigen binding site that binds an extracellular part of CD137 and an antigen binding site that binds an extracellular part of a second membrane protem for use in a method of treatment of cancers in a subject in need thereof. The invention further relates to such multispecific antibodies, as well as methods and other aspects related thereto.SELECTED DRAWING: None

The present invention relates to: an affinity that specifically binds to the extracellular domain of CD137; a protein complex comprising the affinity and an antibody or an antigen-binding fragment thereof that specifically binds to a protein on the surface of cancer cells; and a pharmaceutical composition for preventing or treating cancer, comprising the same as an active ingredient. When using the affinity that specifically binds to CD137 according to the present invention, it is possible to develop a protein complex that specifically binds to antigens on the surfaces of various cancer cells while specifically binding to T cells, and thus can be effectively used in the prevention or treatment of leukemia and solid cancers.

Antibodies that include an antigen binding region that binds to CD137 are provided herein. Also provided herein are bispecific antibodies that include a first antigen binding region that binds to CD137 and a second antigen binding region that binds to an immune checkpoint molecule, an immune stimulatory molecule, or a tumor antigen. Pharmaceutical compositions that include the antibodies and methods of treating cancer are provided.