959 results about "Antigen receptor" patented technology

Provided herein are engineered immune cells and populations thereof for administration to patients to treat cancer (e.g., solid tumors or liquid tumors) and other conditions. The cells are engineered to functionally express a reduced level of one or more of RFX5, NLRC5, TAP2, β2m, TRAC, RFXAP, CIITA and RFXANK. The cells optionally are further engineered to express one or more than one additional protein such as an antigen binding protein (e.g., a chimeric antigen receptor (CAR) or T cell receptor) to target tumor cells or other damaged cells in the patient and / or to express other genes at a reduced level. Also provided are methods of making and using the engineered cells, compositions and kits comprising them, and methods of treating by administering the cells and the compositions.

Provided herein are chimeric cytokine receptors bearing a binding domain capable of binding a TGF-β ligand or a TGF-β receptor antibody. When present on chimeric antigen receptor (CAR)-bearing immune cells (CAR-T-cells), such receptors allow for increased CAR-T cell expansion, activity and persistence, constitutively and / or through engagement of a TGF-β ligand or a TGF-β receptor antibody. Also provided are methods of making and using the chimeric cytokine receptors described herein.

Chimeric antigen receptors targeted to IL-13Ra2 are described. The targeting domain is a IL13 variant having increased specificity for IL-13Ra2 relative to IL-13Ra1.

Provided herein are novel Glypican 3 (GPC3) antibodies or antigen binding fragments and GPC3 / CD3 bispecific antibodies. The present application also provides chimeric antigen receptors comprising the antibodies or antigen-binding fragments, related CAR-T cells, and preparation methods and uses of the same. The present application further provides pharmaceutical compositions comprising GPC3 antibodies or antigen binding fragments, related GPC3 / CD3 bispecific antibodies, related GPC3 CAR or CAR-T cells, and methods of treating cancer in a subject in need thereof by administering the Glypican 3 (GPC3) antibodies or antigen binding fragments, the bispecific antibodies, the chimeric antigen receptors, the CAR-T cells, or the pharmaceutical compositions. The cancers treated in accordance with the application include Glypican-3-positive cancers.

The application provides an application of a FAP-targeted CAR-T cell in preparation of a drug for treating cardiac fibrosis in a chronic phase of myocarditis. It is found in the application that FAP-specific CAR-T cells can effectively target cells expressing mouse FAP proteins, and the CAR-T cells can effectively eliminate cells expressing mouse FAP proteins after being activated, the chimeric antigen receptor T cells effectively reduce cardiac fibrosis in a chronic phase of myocarditis in mice, and restore the function after inflammatory injury. The application develops a CAR-T therapy for myocardial fibrosis caused by a chronic phase of myocarditis, and the chimeric antigen receptor T cells expressing a targeted fibroblast activation protein can recognize activated myocardial fibroblasts, and significantly reduce cardiac fibrosis after inflammatory injury and restore the function.

The present disclosure provides a population of CD4IL-10 / CAR cells (autologous or allogeneic single-donor and allogeneic polydonor) generated by genetically modifying CD4+ Tcells to express IL-10 and a chimeric antigen receptor. Further provided are methods of generating the CD4IL-10 / CAR cells and methods of using the CD4IL-10 / CAR cells for immune tolerization, treating GvHD, cell and organ transplantation, cancer, and autoimmune and inflammatory disorders.

The invention relates to the field of biomedical treatment, and particularly discloses application of CD146 in diagnosis and treatment of rhabdomyosarcoma, and the CD146 is specifically and highly expressed in tumor tissues of the rhabdomyosarcoma. The invention provides application of a biomarker for diagnosing rhabdomyosarcoma or / and a detection reagent thereof in preparation of a product for diagnosing rhabdomyosarcoma. Meanwhile, experiments prove that the CD146-targeted chimeric antigen receptor T cell has a relatively strong tumor cell killing effect and can effectively remove CD146 positive tumor cells. The CD146 biomarker provided by the invention provides a new target and theoretical basis for early diagnosis and individualized treatment of rhabdomyosarcoma, and has important clinical application value.

Embodiments provided herein include methods and compositions comprising anti-dinitrophenol chimeric antigen receptors (CARs). Some embodiments include nucleic acids encoding such CARs, polypeptides encoded by such nucleic acids, cells comprising such nucleic acids or polypeptides, and methods utilizing such cells. Some embodiments also include the use of dinitrophenol (DNP) and derivatives thereof.

Compositions and methods for treating diseases associated with expression of a cancer associated antigen are disclosed. The invention also relates to chimeric antigen receptor (CAR) specific to a cancer associated antigen as described herein, SHP inhibitory molecules, vectors encoding the same, and recombinant immune effector cells comprising the CARs and SHP inhibitory molecules. Methods of administering a genetically modified immune effector cell expressing a CAR that comprises an antigen binding domain that binds to a cancer associated antigen and a SHP inhibitory polypeptide are also disclosed.

The invention is directed to a chimeric antigen receptor (CAR) directed against CD19, which comprises an amino acid sequence of any one of SEQ ID NO: 1-SEQ ID NO: 13. The invention also provides T-cells expressing the CAR and methods for destroying malignant B-cells.

The invention provides compositions and methods for treating diseases associated with expression of CD20 or CD22. The invention also relates to chimeric antigen receptor (CAR) specific to CD20 or CD22, vectors encoding the same, and recombinant T or natural killer (NK) cells comprising the CD20 CAR or CD22 CAR. The invention also includes methods of administering a genetically modified T cell or NK cell expressing a CAR that comprises a CD20 or CD22 binding domain.

Provided herein are compositions of NK-92™ cells that express a combination of PD-L1 CAR, CD16 and IL2, and the method of using these cells to to reduce tumor cells and cells in tumor microenvironment (e.g., MDSCs or TAMs) and treat cancer.

Provided are polypeptides that include, from N-terminus to C-terminus, a chimeric antigen receptor (CAR), a protease, and a degron, where the polypeptide further includes a cleavage site for the protease disposed between the CAR and the degron. Also provided are cells that include such polypeptides (e.g., where the cells express the CAR on their surface) and pharmaceutical compositions including such cells. Nucleic acids that encode the polypeptides, cells including such nucleic acids, and pharmaceutical compositions including such cells, are also provided. Also provided are methods for controlling the expression of a CAR on the surface of a cell, and methods of using the cells of the present disclosure, including methods of using such cells to administer a regulatable CAR cell-based therapy (e.g., a regulatable CAR T cell therapy) to an individual.

Provided herein are compositions of NK-92™ cells that express a combination of PD-L1 CAR, CD16 and IL2, and the method of using these cells to to reduce tumor cells and cells in tumor microenvironment (e.g., MDSCs or TAMs) and treat cancer.

The present invention is directed to a monoclonal anti-human CS1 clone 7A8D5 antibody or a single-chain variable fragment (scFv), comprising VH having the amino acid of SEQ ID NO: 4 and VL having the amino acid of SEQ ID NO: 5. The present invention is also directed to a chimeric antigen receptor fusion protein comprising from N-terminus to C-terminus: (i) CS1 scFv of the present invention, (ii) a transmembrane domain, (iii) at least one co-stimulatory domains, and (iv) an activating domain.

Chimeric antigen receptors for use in treating malignant melanoma and other cancers expressing CS1 are described.

The invention relates to the technical field of nano antibodies, in particular to an anti-FcRH5 nano antibody and application thereof. The invention provides an anti-FcRH5 nano antibody with high affinity and specificity, and the anti-FcRH5 nano antibody is based on a single-domain heavy chain variable region structure from camelidae and has the advantages of small molecular weight, high stability, strong tissue penetrability, easiness in engineering modification and the like. The nano antibody specifically recognizes and is combined with a high-expression and stable-expression target spot on the surface of a multiple myeloma cell through a complementary determining region of the nano antibody. The nano antibody disclosed by the invention can be used as a core recognition element for constructing various treatment or diagnosis tools such as chimeric antigen receptor T cells, bispecific antibodies, antibody drug conjugates or immunodetection probes and the like. According to the technical scheme, the technical problem that an anti-FcRH5 antibody with high quality and definite functionality is lacked in the prior art can be solved. The nano antibody provided by the invention has remarkable clinical transformation and industrialization advantages, and promotes multiple myeloma treatment to multi-target collaborative iteration.

The invention provides an anti-PD-1 antibody, a CAR-T cell, and a preparation method and application thereof. The anti-PD-1 antibody comprises LCDR-1-3 as shown in SEQ ID NO: 1-3 and HCDR-1-3 as shown in SEQ ID NO: 4-6, respectively. The CAR-T cell expresses a novel element for efficiently blocking the PD-1, and the element is a single-chain antibody for targeting the PD-1 in a cell membrane anchoring manner. And the chimeric antigen receptor and the cell membrane anchored anti-PD-1 scFv are connected by a 2A cleavage protein. The membrane anchor type anti-PD-1 scFv expressed by the CAR-T cell can almost completely block the expression of PD-1 on the surface of a T cell membrane, and further block a signal channel combined with PD-1 / PD-L1, so that the capability of T cell depletion caused by antagonism tumor of the CAR-T cell is enhanced, and the purpose of enhancing the anti-tumor effect of the CAR-T cell is achieved.

Disclosed are CAR polypeptides comprising an antigen binding domain, a transmembrane domain, and an intracellular signaling domain, wherein the intracellular signaling domain comprises a variant CD3 zeta (CD3ζ). Disclosed are nucleic acid sequences capable of encoding any of the disclosed CAR polypeptides. Disclosed are vectors comprising the nucleic acid sequence of the disclosed CAR nucleic acid sequences. Disclosed are cells comprising any of the CAR polypeptides, CAR nucleic acid sequences, or vectors disclosed herein. Disclosed are methods of treating a subject having cancer comprising administering a therapeutically effective amount of a composition comprising a T cell genetically modified to express one or more of the CAR polypeptides disclosed herein to the subject having cancer. Disclosed are methods of using one or more of the disclosed CAR polypeptides.

The present invention is directed to a humanized BCMA single-chain variable fragment (scFv), comprising VH having the amino acid sequence of SEQ ID NO: 4 and VL having the amino acid sequence of SEQ ID NO: 5. The present invention is also directed to a BCMA chimeric antigen receptor fusion protein comprising from N-terminus to C-terminus: (i) a single-chain variable fragment (scFv) of the present invention, (ii) a transmembrane domain, (iii) at least one co-stimulatory domains, and (iv) an activating domain. This humanized BCMA-CAR-T cells have specific killing activity with secretion of cytokine IFN-gamma in CAR-T cells in vitro and in vivo.

Novel anti-effector moiety antibodies or antigen binding domains thereof and CARs that contain such effector moiety antigen binding domains, either with or without one or more booster elements, and host cells expressing the receptors, and nucleic acid molecules encoding the receptors are provided herein, as well as methods of use of same in a patient-specific immunotherapy that can be used to treat solid tumor cancers and other diseases and conditions.

Provided are the construction, preparation and use of a functionally enhanced universal CAR-DNT cell. Specifically, provided is a chimeric antigen receptor construct. A CAR function-enhancing element and IL-10 are sequentially fused to the C-terminus of a tumor antigen-targeting CAR via a self-cleaving peptide, and the CAR construct is introduced into a DNT cell, thereby obtaining a functionally enhanced universal CAR-DNT cell, namely, an IL10-CD19-CAR-mbIL15-DNT cell. The cell specifically targets CD19, and has a stronger and more sustained cell killing activity and better safety, thus providing a new therapy for CD19-mediated diseases.

Disclosed herein are VH-only single domain binders that target claudin 18.2 (CLDN18.2) and chimeric antigen receptors (CARs) that contain the same, engineered T cells containing the CLDN18.2-targeting CARS, and methods of treating cancer (e.g., gastric cancer or pancreatic cancer) using the CAR-T cells.

Chimeric antigen receptors (CARs) and bicistronic chimeric antigen receptors (BiCisCARs) that target fibroblast growth factor receptor 4 (FGFR4), CD276, or both are disclosed. The CARs and BiCisCARs include a hinge and transmembrane domain from either CD28 or CD8 and a co-stimulatory domain from either CD28 or 4-1BB. The CARs and BiCisCARs can further include amino acid substitutions in one or more immunoreceptor tyrosine-based activation motifs (ITAMs) of a CD3ζ intracellular signaling domain. Cells expressing the CARs or BiCisCARs can be used for the treatment of cancers that express one or both of FGFR4 and CD276.

The invention relates to a CD19 and CD70 targeted double-target chimeric antigen receptor and application thereof, the CD19 and CD70 targeted double-target chimeric antigen receptor comprises an extracellular antigen binding domain, a hinge region, a transmembrane domain, an intracellular costimulatory domain and an intracellular signal transduction domain, and the extracellular antigen binding domain has specific binding ability to CD19 and CD70. The double-target chimeric antigen receptor structure has a treatment effect of targeting double antigens or single antigens, can be used for preparing immune effector cells targeting CD19 and CD70, and provides a treatment or improvement approach for diseases related to CD19 and CD70 double expression or CD19 / CD70 single expression.

Provided are humanized nanobody targeting BCMA and a use thereof. The nanobody is capable of binding to B-cell maturation antigen (BCMA), and the isolated antigen-binding protein comprises at least one CDR in an antibody heavy chain variable region (VH). Provided are a chimeric antigen receptor, a fusion protein, a cell and a nucleic acid molecule comprising the antigen-binding protein, and a use thereof in the treatment of tumors.

The disclosure provides for various methods including a method of reducing the severity of bispecific T cell engager (BiTE) or chimeric antigen receptor T cell (CAR-T) induced cytokine release syndrome (CRS) comprising administering to a patient in need thereof an amount of a composition comprising an interleukin 10 (IL-10) or an IL-10 agent, an interleukin 4 (IL-4) or an IL-4 agent, or combinations thereof.

Provided are therapeutic agent including nucleic acid and CAR-modified immune cell and the use thereof. The therapeutic agent comprises first composition and second composition, the first composition comprises a nucleic acid having a labeling polypeptide coding sequence for being introduced into a tumor cell and / or a cancer cell; the labeling polypeptide has an extracellular antigen determining region, a spacer portion, a transmembrane portion that are operatively linked, which can be expressed to form modification on the surface of the tumor cell and / or cancer cell; the extracellular antigen determining region comprises one or more epitope polypeptides; wherein, amino acid sequences of proteins on cell membrane or secreted proteins of mammal do not comprise the epitope polypeptide amino acid sequence in the natural state; the second composition comprises chimeric antigen receptor modified immune cell which specifically recognize and bind to the extracellular antigen determining region. The therapeutic agent achieves synergistic therapeutic effect.

This document provides methods and materials involved in treating cancer. For example, chimeric antigen receptor T cells having reduced levels of GM-CSF are provided. Also provided as methods for making and using chimeric antigen receptor T cells having reduced levels of GM-CSF.

Provided are an anti-DLL3 antibody or an antigen-binding fragment thereof, a chimeric antigen receptor and a mutant thereof, and an enhanced chimeric antigen receptor comprising a PDL1 antagonist and an mIL7 element. Further provided are a nucleic acid encoding same, an expression cassette, vector and cell comprising the nucleic acid, a preparation method, and a use for preventing, treating, detecting, or diagnosing diseases related to DLL3. In the enhanced DLL3 chimeric antigen receptor, the PDL1 antagonist and the cell membrane IL7 cytokine element play a critical role in a long-term anti-tumor process. Animal efficacy experiments have shown complete tumor regression in all mice, indicating broad application prospects in the pharmaceutical field.