51 results about "Mesothelin" patented technology

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.

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.

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 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.

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 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 is directed to antibodies, including novel antigen binding domains and heterodimeric antibodies, that bind Mesothelin (MSLN).

The present invention relates to CAR-expressing immune cells for improving cancer treatment and immunotherapy efficacy. More specifically, the present invention provides immune cells expressing a bispecific CAR (biCAR) that targets both endoglin and mesothelin, and thus is expected to be used as an immunotherapeutic agent capable of reducing immunosuppression by CAF in a tumor microenvironment and effectively killing cancer cells.

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

A recombinant vector, a lentivirus, a lung-exempt MSLN CAR-T cell, and an anti-tumor agent are provided. The recombinant vector includes a first nucleotide sequence, a second nucleotide sequence, and a third nucleotide sequence, the first nucleotide sequence encodes a mesothelin (MSLN)-binding domain, the second nucleotide sequence encodes a leukocyte immunoglobulin-like receptor (LIR-1), and the third nucleotide sequence specifically binds to a lung-highly-expressed molecule. The lentivirus is constructed using the recombinant vector. The lung-exempt MSLN CAR-T cell is constructed using the recombinant vector or the lentivirus. When the lung-exempt MSLN CAR-T cell enters lung tissue, the second nucleotide sequence binds to the lung-highly-expressed molecule through the third nucleotide sequence, inhibiting the killing function of CAR-T to avoid pulmonary toxicity; when the lung-exempt MSLN CAR-T cell infiltrates tumor tissue, the second nucleotide sequence is inactivated, activating CAR-T cells to kill tumor cells, offering the advantages of precise therapy and low side effects.

The disclosure provides scFv molecule that specifically bind mesothelin, chimeric antigen receptors that comprise antigen-binding domains comprising the scFv, nucleotides that encode the same, cells comprising the same, and methods of using the same in the treatment of cancer.

Antibodies, antigen-binding fragments, and conjugates (e.g., antibody-drug conjugates such as those comprising eribulin) thereof that bind to mesothelin are disclosed. The disclosure further relates to methods and compositions for use in the treatment of cancer by administering the compositions provided herein.

Disclosed herein are MSLN binding proteins having improved binding affinity and improved ability to mediate T cell dependent killing of mesothelin-expressing cancer cells. Further provided are pharmaceutical compositions comprising the binding proteins disclosed herein and methods of using such formulations.

The presently disclosed subject matter provides methods for treating neoplasia using cells comprising an antigen-recognizing receptor (e.g., a chimeric antigen receptor (CAR)) that specifically targets mesothelin.

Provided herein are engineered immune cells and methods of using the same. In embodiments, engineered immune cells bind mesothelin or other protein differentially expressed in cancer. In embodiments, the methods include methods of treating cancer.

Single domain VHH polypeptides (antibodies) that bind mesothelin, VHH polypeptide products, methods, cells, pharmaceutical compositions, and kits. The VHH polypeptides may be recombinantly produced and expressed. Provided are also chimeric antigen receptor (CAR) polypeptides comprising the VHH polypeptides and CAR immune effector cells comprising the expressing the same.

Nucleic acid constructs encoding a chimeric antigen receptor (CAR) and a truncated human epidermal growth factor receptor (huEGFRt) are described. The encoded CAR includes a tumor antigen specific monoclonal antibody, such as a glypican-3 (GPC3)-specific, GPC2-specific or mesothelin-specific monoclonal antibody, fused to a CD8 [alpha] hinge region, a CD8 [alpha] transmembrane region, a 4-1BB co-stimulatory domain, and a CD3 [zeta] signaling domain. Also described are isolated host cells, such as isolated T cells that co-express the disclosed CAR and huEGFRt. The T cells transduced with the disclosed CAR constructs can be used in cancer immunotherapy.