75 results about "CD137" patented technology

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.

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 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 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.

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 disclosure provides fusion proteins specific for both CD137 and GPC3, which fusion protein can be used to co-stimulate lymphocyte activation in a GPC3-target-dependent manner. Such fusion proteins can be used in many pharmaceutical applications, for example, as anti-cancer agents and / or immune modulators for the treatment or prevention of human diseases such as a variety of tumors. The present disclosure also concerns methods of making the fusion proteins described herein as well as compositions comprising such fusion proteins. The present disclosure further relates to nucleic acid molecules encoding such fusion proteins and to methods for generation of such fusion proteins and nucleic acid molecules. In addition, the application discloses therapeutic and / or diagnostic uses of such fusion proteins as well as compositions comprising one or more of such fusion proteins.

The present application relates to dosage regimes for the administration of an antigen-binding protein which binds CD137 and programmed death-ligand 1 (PD-L1) and their use in the treatment of cancer in human patients.

To provide antigen-binding domains binding to CD3 and CD137 and methods of using the same, and also provide methods to obtain antigen binding domains which bind to two or more different antigens more efficiently.SOLUTION: The present invention provides antigen-binding molecules, comprising: an antibody variable region that is capable of binding to CD3 and CD137, but does not bind to CD3 and CD137 at the same time; and a variable region binding to a third antigen different from CD3 and CD137.SELECTED DRAWING: Figure 1

The invention provides a multiplication culture method of high-purity memory NK cells, which comprises the following steps: in the initial stage of cell culture, adopting a CD6 antibody, an ADAM inhibitor, IL2, IL15 and IL18 as a starting signal combination; furthermore, a CD137 antibody, IL2 and IL21 are adopted as an amplification signal combination, IL2, IL15 and IL21 are supplemented regularly, and NK amplification is promoted. According to the invention, multiple factors and antibody combination are originally utilized, so that NK cell culture and / or NK cell amplification can be more efficiently started; the memory NK cell prepared by the method has the characteristics of high purity and high amplification multiple of NK, and has high killing ability.

The present invention relates to novel binding agents and their use in medicine. In particular, the invention relates to binding agents such as bispecific antibodies binding human PD-L1 and binding human CD137. The invention furthermore relates to uses of the antibodies of the invention and to methods, nucleic acid constructs and host cells for producing antibodies of the invention.

The present disclosure provides use of a binding agent that binds to EpCAM and CD137 in combination with a PD-1 axis binding antagonist in the treatment or prevention of a tumor or cancer, or in the prevention of progression of a tumor or cancer.

The present invention relates to a combination therapy of an anti-EGFRvIII / anti-CD3 bispecific antibody with a tumor targeting 4-1BB (CD137) agonist.

The application provides a bicyclic compound with a structure shown in formula (I) or a pharmaceutically acceptable salt, a stereoisomer or a prodrug molecule thereof, a pharmaceutical composition and application. The compound provided by the application can activate CD137, enhance the immune function of cytotoxic T lymphocytes (CTL), enhance the memory function of CD8+ T cells and CD4+ T cells, can make the polarization of CD4+ T cells tilt to a state beneficial to cellular immunity, and can promote the multimerization of CD137, so that T cell immunity can be effectively activated, the volume of a primary tumor can be effectively reduced, and the compound can be used for inhibiting and treating tumors.

The present invention relates to a tumor-reactive T cell composition obtained by expansion from a patient sample, wherein upon stimulation with tumor cell antigens, the proportion of CD8+CD137+ cells among CD45+ cells in the composition is at least greater than 25%, and / or the proportion of CD45RA+CD62L+ cells in the composition is at least greater than 30%. The present invention further relates to a method for obtaining a tumor-reactive T cell composition by expansion from a patient sample. Tumor-reactive T cells in the composition of the present invention have a high total count, a long lifespan, a high viability rate, and a potent tumor-killing capacity, thereby providing a basis for the use of the composition in tumor therapy.

The disclosure provides a fusion polypeptide specific for CD137 and GPC3, which fusion polypeptide may be useful for directing CD137 clustering and activation of GPC3-positive cancer cells. Such a fusion polypeptide may be useful in many pharmaceutical applications, for example, as an anticancer agent and / or immunomodulator for the treatment or prevention of human diseases, such as a variety of cancers. The disclosure also relates to methods of making the fusion polypeptide described herein, as well as compositions comprising such a fusion polypeptide. The disclosure further relates to nucleic acid molecules encoding such a fusion and nucleic acid molecules. Furthermore, the disclosure includes therapeutic and / or diagnostic uses of such a fusion polypeptide, as well as compositions comprising one or more such fusion polypeptides.

The present invention provides a binding agent that binds to EpCAM and to CD137 which is useful to treat or prevent a tumor or cancer, or to prevent progression of a tumor or cancer.

The invention relates to a triple-effect T cell adapter for targeting T cell lymphoma TRBC1. The invention discloses a TRBC1-targeted triple-effect T cell adapter which is composed of an Fc region, a hinge region, a first Fab arm and a second Fab arm, and a third targeting module is covalently connected to the C end of the Fc region to form a Y-shaped triple-head antibody. The first Fab arm and the second Fab arm are respectively combined with TRBC1 and CD3, and the third Fab arm is combined with CD28 or CD137, so that three functions of tumor recognition, T cell recruitment and co-stimulation amplification are integrated. The two polypeptide chains are heterodimerized through CH3 region button mutation, and correct assembly is ensured. The structure supports module interchange, programmable regulation and control of synergistic signals, significantly enhances TRBC1 positive T cell lymphoma killing, reduces toxicity to normal T cells, has high activity and a wide safety window, and is suitable for preparation of related drugs.

The present disclosure relates to a method of treating non-small cell lung cancer in human subjects using a combination therapy of a bispecific antibody binding to PD-L1 and to CD 137 and a PD-1 antagonist.