98 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.

Antibodies and antigen-binding fragments thereof that bind to human mesothelin have been described.

The present invention relates to a pharmaceutical composition and a use thereof, and specifically provides a pharmaceutical composition, comprising: a cell and a pharmaceutically acceptable adjuvant. The adjuvant comprises a diluent and a cryoprotectant; the cell is a T cell containing and / or expressing a 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; CDR2 comprises a sequence as shown in SEQ ID NO: 2; and CDR3 comprises a sequence as shown in SEQ ID NO: 3.

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.

Some aspects of the present disclosure are directed to engineered innate lymphoid cells comprising a heterologous targeting construct specific for mesothelin and uses thereof. Some aspects of the present disclosure are directed to polynucleotides encoding a chimeric antigen receptor (CAR) that specifically binds human mesothelin, host cells comprising the polynucleotide, and methods of treating a disease or condition in a subject using the same.

The present invention relates to antibody arms that bind to human CD28 agonists. The present invention relates to bispecific antibodies that bind to human carcino-embryonic antigen (CEA) and human CD28 using the agonist anti-CD28 arm described herein. The present invention relates to bispecific antibodies that bind to human mesothelin (MSLN) and human CD28 with the anti-CD28 arm using the agonist described herein.

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 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 application relates to mesothelin-targeting CD40 agonistic multispecific antibody constructs for the treatment of solid tumors. Specifically, the present application relates to human agonistic CD40 multispecific antibody constructs for use in the treatment of solid tumors by engineering molecules that specifically target the CD40 pathway on tumor-associated APCs without the need for systemic CD40 activation.

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.

Provided are compositions and methods for treating diseases associated with expression of mesothelin. Also provided are a chimeric antigen receptor (CAR) specific to mesothelin, vectors encoding the same, and recombinant T cells comprising the mesothelin CAR. Further provided are methods of administering a genetically modified T cell expressing a CAR that comprises a mesothelin binding domain.

Polypeptides, proteins, and chimeric antigen receptors (CARs) that specifically bind to human mesothelin582-598 (IP-NGYLVLDLSMQEALS) (SEQ ID NO: 1) are disclosed. Anti-mesothelin binding moieties, nucleic acids, recombinant expression vectors, host cells, populations of cells, pharmaceutical compositions, and conjugates relating to the poly peptides, proteins, and CARS are disclosed. Methods of reducing mesothelin shed from cell membranes, methods of detecting the presence of cancer, and methods of treating or preventing cancer are also disclosed.

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 invention discloses a cell engineering method for reversing PD1 signals of T and CAR-T cells by using CD27. Specifically, the invention discloses a fusion protein PD1-CD27 (SEQ ID No. 4) and a nucleic acid molecule (SEQ ID No. 1), and further constructs a modified T cell for different antigens. The modified T cell has small influence on the phenotypes of CD4 and CD8-T cells of a patient, the proportion of memory T cells is increased, and the modified T cell can survive for a long time, specifically recognizes and kills tumor cells expressing tumor-associated antigens (mesothelin, HER2 and the like), has no killing effect on negative cells, and has the effects of resisting a tumor cell microenvironment and resisting T cell depletion. The CD27 is used for reversing an inhibition signal of PD1, and the CD27 has practical significance and potential clinical application value for overcoming a tumor microenvironment, playing a cytotoxic role in the microenvironment and prolonging the survival time of CAR-T.

Provided are compositions and methods for treating diseases associated with expression of mesothelin comprising administering a cell that expresses a chimeric antigen receptor (CAR) specific to mesothelin in combination with a PD-L1 inhibitor.

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.

The present disclosure provides immune cells comprising a first activating receptor specific for mesothelin and a second inhibitory receptor specific for a ligand that is lost in mesothelin-positive cancer cells, and methods of making and using said immune cells for the treatment of cancer. Provided herein are compositions and methods related to the treatment of MSLN(+) cancer. Advantageously, the compositions and methods disclosed herein can take advantage of loss of heterozygosity (LOH) to address MSLN(+) cancer.