76 results about "Mesothelin" patented technology

The present invention relates to recombinant binding proteins comprising an ankyrin repeat domain with binding specificity for soluble mesothelin or membrane-bound mesothelin. In addition, the invention relates to nucleic acids encoding such recombinant binding proteins, pharmaceutical compositions comprising such proteins or nucleic acids, and the use of such binding proteins, nucleic acids or pharmaceutical compositions in methods for treating or diagnosing diseases, such as cancer in a mammal, including a human.

The present invention relates to an antibody or an antigen-binding fragment thereof comprising a single domain antibody specifically binding to mesothelin, an antibody conjugate comprising same, a pharmaceutical composition for preventing or treating cancer or a tumor, and a composition for diagnosing or monitoring cancer or a tumor. When the antibody or composition comprising same is used, mesothelin-related cancer or tumors can be effectively prevented, treated, or diagnosed.

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 present disclosure relates to mesothelin chimeric antigen receptors (CARs), T cell engaging molecules (TEAMs), anti-mesothelin-CAR T cells optionally comprising TEAMs, and methods of use thereof.

The present invention relates to MSLN-specific binding constructs comprising a designed ankyrin repeat domain with binding specificity for MSLN and a chelator capable of bonding to a radionuclide, as well as to such MSLN-specific binding constructs comprising a half-life extending moiety with binding specificity for serum albumin. The invention further relates to methods of producing such radio-labelled MSLN-specific binding constructs, pharmaceutical compositions comprising such constructs, and the use of such constructs or pharmaceutical compositions in methods for treating, imaging or diagnosing diseases, such as cancer.

The present application provides constructs comprising an antibody moiety that specifically binds to a mesothelin extracellular domain. Also provided are methods of making and using these constructs, and uses thereof, including treating and diagnosing diseases.

Relates to a pharmaceutical composition and application thereof, in particular to a pharmaceutical composition which comprises cells and pharmaceutically acceptable auxiliary materials, the auxiliary materials comprise a diluent and a cryoprotective agent, the cells are T cells containing and / or expressing a chimeric antigen receptor and / or containing a coding sequence of the chimeric antigen receptor, and the T cells are T cells containing and / or expressing the chimeric antigen receptor and / or containing a coding sequence of the chimeric antigen receptor. An antigen binding domain of the chimeric antigen receptor comprises a mesothelin binding molecule containing an anti-mesothelin single domain antibody, the anti-mesothelin single domain antibody comprises CDR1, CDR2 and CDR3, the CDR1 comprises a sequence as shown in SEQ ID NO: 1, the CDR2 comprises a sequence as shown in SEQ ID NO: 2, and the CDR3 comprises a sequence as shown in SEQ ID NO: 3.

The present invention relates to engineered immune cells expressing a chimeric antigen receptor (anti-mesothelin CAR) specific for mesothelin (MLSN) and their use in the treatment of solid tumors, particularly suitable for allogeneic cell immunotherapy.

The present invention relates to the technical field of immunotherapy. The present invention provides a single-domain antibody targeting mesothelin, a chimeric antigen receptor (CAR) targeting mesothelin constructed using the single-domain antibody, and an engineered immune effector cell comprising the CAR. The present invention also provides the use of the single-domain antibody targeting mesothelin, the chimeric antigen receptor, and the engineered immune effector cell comprising the CAR in the preparation of a medicament for diagnosing, preventing, and / or treating a disease or disorder associated with mesothelin expression.

Mesothelin-binding fibronectin type III (Fn3) domain proteins having improved mesothelin binding characteristics are described.

The present invention relates to engineered immune cells expressing novel mesothelin (MLSN)-specific chimeric antigen receptors (anti-mesothelin CARs) and their use in the treatment of solid tumors, particularly for allogeneic cellular immunotherapy.

The application discloses a nanobody targeting mesothelin and application thereof, and belongs to the technical field of molecular biology. In view of the unique advantages of nanobodies in the prior art, the application provides a nanobody targeting mesothelin, wherein the nanobody targeting mesothelin comprises CDR1 as shown in SEQ ID NO. 1, CDR2 as shown in SEQ ID NO. 2 and CDR3 as shown in SEQ ID NO. 3. The nanobody targeting mesothelin has strong binding force with cells overexpressing mesothelin. It can be seen that the nanobody targeting mesothelin can bind to mesothelin protein expressed on the surface of cells, and can be applied to preparation of a protein detection antibody or a therapeutic antibody, and has important commercial value in clinical disease diagnosis and treatment.

The present disclosure relates to methods of treating patients using anti-mesothelin- CAR-T cells comprising anti-fibroblast activation protein (FAP) TEAMs, and ADAM 17 or ITK inhibitors.

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.

Mesothelin-binding fibronectin type III (Fn3) domain proteins having improved mesothelin binding characteristics are described.

Provided is an anti-mesothelin chimeric antigen receptor that has increased affinity for mesothelin and binds specifically to mesothelin. An anti-mesothelin chimeric antigen receptor according to one aspect has increased affinity for mesothelin and exhibits a specific binding ability to mesothelin, and accordingly, can be useful for the prevention or treatment of cancer in which mesothelin is overexpressed.

Nucleic acid constructs encoding chimeric antigen receptors (CARs) and truncated human epidermal growth factor receptors (huEGFRt) are described. The encoded CARs include tumor antigen-specific monoclonal antibodies fused to CD8α hinge regions, CD8α transmembrane regions, 4-1BB costimulatory domains, and CD3ζ signaling domains, such as glypican-3 (GPC3)-specific, GPC2-specific, or mesothelin-specific monoclonal antibodies. Separated host cells are also described, such as separated T cells co-expressing the disclosed CARs and huEGFRt. T cells transduced with the disclosed CAR constructs can be used for cancer immunotherapy.

To provide an isolated nucleic acid molecule encoding a chimeric antigen receptor specific to mesothelin.SOLUTION: The present invention provides an isolated nucleic acid molecule encoding a chimeric antigen receptor. The chimeric antigen receptor comprises (i) a human anti-mesothelin binding domain comprising light chain complementary determining regions 1, 2, 3, comprising specific amino acid sequences, and heavy chain complementary determining regions 1, 2, 3, comprising specific amino acid sequences; (ii) a transmembrane domain; and (iii) an intracellular signaling domain comprising a stimulatory domain.SELECTED DRAWING: None

The present disclosure provides mesothelin (MSLN)-specific nanobodies, CEACAM5-specific nanobodies, bispecific MSLN / CEACAM5 antibodies, and chimeric antigen receptors (CARs), including bispecific CARs therefrom. The disclosure further provides CAR T / NK cells and methods of treatment with antibodies and CAR T / NK cells described herein.

An object according to certain aspect(s) of the present invention is to provide an immunocompetent cell that expresses regulatory factors of immunocompetent cell immune function and possesses all of proliferative potential, viability, and the ability to accumulate a T cell, and an expression vector of regulatory factors of immune function for generating the immunocompetent cell. An immunocompetent cell expressing a cell surface molecule specifically recognizing a cancer antigen, interleukin 7 (IL-7), and CCL19 is generated. Preferably, the cell surface molecule specifically recognizing a cancer antigen is T cell receptor specifically recognizing the cancer antigen, and the immunocompetent cell is a T cell. Another object according to certain aspect(s) of the present invention is to provide an immunocompetent cell targeting mesothelin. An immunocompetent cell that expresses a cell surface molecule specifically recognizing human mesothelin, interleukin 7 (IL-7), and chemokine (C-C motif) ligand 19 (CCL19) is produced. It is preferred that: the cell surface molecule specifically recognizing human mesothelin should be chimeric antigen receptor (CAR) having single chain antibody, a transmembrane region, and a signaling region that induces the activation of the immunocompetent cell; and the heavy chain variable region and the light chain variable region should be connected via a peptide linker consisting of a 2- to 30-amino acid sequence.

Mesothelin-binding theranostic fibronectin type III (Fn3) domain polypeptides conjugated to DOTAGA are described.

Methods and materials for reducing the level of circulating extracellular mesothelin (also referred to herein as soluble MSLN or sMSLN) by therapeutic plasma exchange (TPE) are provided herein. For example, methods and materials for using TPE to reduce the level of sMSLN in mammals (e.g., humans) identified as having mesothelioma or another solid tumor are provided herein.

The present invention provides novel human antibodies that specifically bind to MUC16 as well as novel human antibodies that specifically bind to Mesothelin. The present invention further relates to complementary pairs of CyCAT halfbody molecules encompassing the novel MUC16 and Mesothelin specific antibodies of the present invention and their use in redirecting T-cell mediated killing of MUC16 / Mesothelin co-expressing cancer cells, via on-target on-cell formation of T-cell engaging trispecific antibodies.

The present invention relates to a human agonistic CD40 multispecific antibody construct for treatment of solid tumors by engineering a molecule that specifically targets the CD40 pathway on tumor-associated APCs, without systemic CD40 activation.

The present invention relates to a human agonistic CD40 multispecific antibody construct for treatment of solid tumors by engineering a molecule that specifically targets the CD40 pathway on tumor-associated APCs, without systemic CD40 activation.

Binding proteins specific for Msln20-28 or Msln530-538 peptides are provided herein. Polynucleotides encoding the binding proteins, as well as compositions and recombinant host cells comprising the binding proteins or polynucleotides are also provided. The compositions and recombinant host cells may be used to treat a subject having mesothelioma, pancreatic cancer, ovarian cancer, lung cancer, a cancer wherein an Msln20-28 peptide is expressed on a tumor cell of the cancer, or a cancer wherein an Msln530-538 peptide is expressed on a tumor cell of the cancer.

This invention provides antibodies targeting MSLN, as well as multispecific antibodies, chimeric antigen receptors, antibody-drug conjugates, pharmaceutical compositions and kits comprising them, and their use in the diagnosis / treatment / prevention of diseases associated with MSLN expression.

The present invention comprises human antibodies that bind to mesothelin (MSLN) protein. These antibodies can be used to treat cancer.

An isolated antigen binding protein capable of targeting MSLN. The isolated antigen binding protein comprises at least one CDR in an antibody heavy chain variable region VH, and the VH comprises an amino acid sequence as set forth in any one of SEQ ID NO: 8, SEQ ID NO: 13, SEQ ID NO: 69, and SEQ ID NO: 70. Also provided are a chimeric antigen receptor comprising the antigen binding protein, and use of the antigen binding protein in treating tumors.

The present disclosure relates, in general, to methods for generating engineered antigen-specific T cell receptors, cells and non-human animals comprising such engineered T cell receptors and methods of making engineered T cell receptors. The engineered T cell receptors can be specific for cancer or immunology targets, such as mesothelin, and are useful in developing therapies for cancer, autoimmune diseases, infectious diseases and other conditions or disorders.