600 results about "Chimeric 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.

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.

The present invention relates to an antibody or an antigen-binding fragment thereof binding to CLDN18.2, an antibody-drug conjugate comprising same, and a use of the antibody and the antibody-drug conjugate. An anti-CLDN18.2 monoclonal antibody according to the present invention comprises a fully human antibody sequence, thereby having low in vivo immunogenicity, and exhibits excellent antigen affinity and binding ability specific to a low expression to a high expression level of the CLDN18.2 protein. Thus, the antibody is expected to exhibit high specificity and safety as an antibody-based therapeutic agent such as in the form of a monoclonal antibody and / or an antigen-binding fragment (scFv), an antibody-drug conjugate (ADC), an immune cell engager, a chimeric antigen receptor (CAR), a multispecific antibody, and the like. In addition, the antibody according to the present invention may undergo cellular internalization, enables an anti-CLDN18.2 antibody-drug conjugate comprising said antibodies to be conveniently prepared, and has excellent yield and quality and thus is expected to be highly likely to be developed as a drug. A drug conjugate comprising the anti-CLDN18.2 antibody according to the present invention has excellent in vivo anticancer efficacy and has an expanded therapeutic index (TI) and thus is expected to be usefully employable for the treatment and / or prevention of cancer diseases expressing CLDN18.2 and related diseases.

Genetically engineered immune cells, which express at least two metabolism modulating polypeptides and optionally a chimeric receptor polypeptide (e.g., an antibody-coupled T cell receptor (ACTR) polypeptide or a chimeric antigen receptor (CAR) polypeptide) capable of binding to a target antigen of interest. Also disclosed herein are uses of the engineered immune cells for inhibiting cells expressing a target antigen in a subject in need thereof.

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.

The present invention relates to: a receptor tyrosine kinase like orphan receptor 1 (ROR 1) antibody or an antigen-binding fragment thereof; a nucleic acid encoding same; a recombinant expression vector carrying the nucleic acid; a host cell transinfected with the recombinant expression vector; a method for preparing the antibody or the antigen-binding fragment thereof; a bi- or multi-specific antibody bearing the antibody or the antigen-binding fragment thereof; an immune cell-engaging bi- or multi-specific antibody; an antibody-drug conjugate (ADC) in which the antibody or the antigen-binding fragment thereof is bound to a drug; a chimeric antigen receptor (CAR) containing the scFv of the antibody as an antigen-binding site of an extracellular domain; an immune cell having the chimeric antigen receptor introduced thereinto; a composition for combination therapy including the antibody or the antigen-binding fragment thereof; a composition for preventing or treating cancer; and a method for preventing or treating cancer.

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.

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

The present invention relates generally to the use of LSD1 inhibitors in connection with use and manufacture of immune effector cells (e.g., T cells, NK cells), e.g., engineered to express a chimeric antigen receptor (CAR), to treat a subject having a disease, e.g., a disease associated with expression of a tumor antigen.

Several embodiments of the methods and compositions disclosed herein relate to immune cells that are engineered to express chimeric antigen receptors as well as genetically edited or otherwise engineered enhance the persistence the cells in immunotherapy. In several embodiments, the cells are edited to knock out a target gene that encodes a protein involved in antigen processing and presentation by major histocompatibility complex class I molecules. In several embodiments, a mixture of immune cell types is used, optionally in allogeneic therapy. The engineering and editing of the cells, such as NK cells and / or T cells exhibit enhanced cytotoxicity and / or persistence, as well as reduced risk of reduced graft versus host, host versus graft, and graft versus graft effects.

A method for treating tumors using a combination of an oncolytic virus vaccine and immune cells. The method specifically includes the following step: treating the tumors by using a combination of the immune cells and the oncolytic virus vaccine; the oncolytic virus vaccine includes a recombinant oncolytic virus expressing a tumor antigen and is used for targeting the tumor cells; the immune cells express a chimeric antigen receptor paired with the tumor antigen, and are used for killing or destroying the tumor cells targeted; the recombinant oncolytic virus includes an M protein, G protein, N protein, P protein and L protein subjected to site-directed mutagenesis. The tumor antigen expressed by the oncolytic virus vaccine can guide the immune cells to reach the target tumor tissue center, achieving a curative effect where 1+1 is greater than 2, with a tumor cell killing rate being up to 100% at most.

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.

Provided are anti-Claudin-6 antibodies (e.g., VHH domain antibodies), and a chimeric antigen receptor (CAR) that binds to Claudin-6 comprising same in an extracellular antigen binding domain, a transmembrane domain, and an intracellular signaling domain. Immune effector cells transduced with the disclosed CAR constructs can be used for cancer immunotherapy.

Disclosed herein are engineered neutrophil extracellular vesicles comprising a cancer- or tumor cell-targeting Chimeric antigen receptor, a therapeutic composition, and at least one miRNA. Also disclosed herein are methods of reducing or inhibiting growth of a cancer or tumor by administering to a subject positive for the cancer or tumor the engineered neutrophil extracellular vesicles disclosed herein.

The present invention relates to the field of immunology and the treatment of diseases. In particular, the present invention relates to an anti-CLDN18.2 antibody or antigen-binding fragment thereof, a nucleic acid molecule encoding it, an immunoconjugate, a bispecific molecule, a chimeric antigen receptor, and a pharmaceutical composition comprising it, and its uses for the prevention and / or treatment of a tumor.

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.

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.

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.

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.

The present invention relates to compositions and methods for generating a modified T cell with a nucleic acid capable of downregulating endogenous gene expression selected from the group consisting of TCR α chain, TCR β chain, beta-2 microglobulin and FAS further comprising a nucleic acid encoding a modified T cell receptor (TCR) comprising affinity for a surface antigen on a target cell or an electroporated nucleic acid encoding a chimeric antigen receptor (CAR). Also included are methods and pharmaceutical compositions comprising the modified T cell for adoptive therapy and treating a condition, such as an autoimmune disease.

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.

Provided herein are engineered T cell receptor (TCR) proteins, nucleic acids, vectors, host cells, methods of treating atherosclerosis-related autoimmune disease, and chimeric antigen receptor expressing T cell (CAR-T) comprising a beta chain CDR3 selected from the amino acid sequence of SEQ ID NOS: 179 to 356 and an alpha chain, wherein the TCR is specific for a human apolipoprotein B (ApoB) epitope, antigen-MHC binding portions, and full-length versions of the same.

The invention provides a chimeric antigen receptor for regulating and controlling a signal time sequence and application of the chimeric antigen receptor. The chimeric antigen receptor sequentially comprises a signal peptide, an extracellular domain, a transmembrane domain and an intracellular domain from an N terminal to a C terminal, the extracellular structural domain comprises an antigen recognition region and a hinge region; the intracellular domain comprises a costimulatory signal transduction region and a CD3 [zeta] intracellular region variant; the CD3 [zeta] intracellular region variant comprises three ITAMs, and the arrangement sequence of the ITAMs is ITAM3-ITAM2-ITAM1 from the N end to the C end. Compared with a conventional chimeric antigen receptor containing a wild CD3 zeta intracellular region, the chimeric antigen receptor provided by the invention can significantly enhance the functional activity of immune cells expressing the chimeric antigen receptor, which is specifically embodied in stronger multiplication capacity and durability, and significantly improves the antigen sensitivity and targeted killing efficacy.

The application provides a nanobody targeting human transmembrane activator and calcium modulator and cyclophilin interactor (TACI) and an application thereof, and the antibody is derived from a llama heavy chain antibody variable region. The anti-TACI single-domain antibody NB38 can specifically bind to human TACI with high affinity, can recognize a recombinant TACI protein, can also recognize a TACI with a natural conformation on a cell surface, and can partially block a BAFF / APRIL signal pathway. Based on the nanobody, the application constructs a fusion protein, a chimeric antigen receptor, an effector cell expressing the chimeric antigen receptor, and a double-specific cell linker and other genetically engineered forms. The nanobody can be further extended into a drug coupling form. The product of the application can be used for mediating directional recognition and killing of TACI positive cells, and can be used as a supplement and expansion of BCMA targeted therapy, and provides a new candidate technical scheme for targeted therapy of multiple myeloma and other TACI related diseases.

This document provides methods and materials involved in treating myeloid neoplasms (e.g., myeloid cancers such as acute myeloid leukemia (AML)). For example, methods and materials for making and / or using T cells expressing (e.g., engineered to express) (a) one or more chimeric antigen receptors (CARs) having the ability to bind to a myeloid-specific polypeptide (e.g., a CD33 polypeptide) and (b) one or more inhibitory CARs (iCARs) having the ability to bind to a class I major histocompatibility complex (MHC) polypeptide (e.g., an HLA-A polypeptide such as an HLA-A2 polypeptide). In some cases, T cells provided herein can be administered to a mammal (e.g., a human) having a myeloid neoplasm (e.g., a myeloid cancer such as AML) and having received a haploidentical bone marrow transplant to target (e.g., target and destroy) the mammal's myeloid cells while sparing the donor-derived myeloid cells.

This invention relates to antigen-binding molecules that specifically bind to ALPPL2 and / or ALPP but not ALPL or ALPI. The invention also relates to pharmaceutical compositions, immunoconjugates, and chimeric antigen receptors comprising said antigen-binding molecules. Furthermore, the invention relates to methods for reducing the expression or activity of ALPPL2 in cancer cells, and methods for treating cancer in subjects.

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.

Provided is a chimeric antigen receptor (CAR) or a T cell receptor (TCR) comprising one or more of the antigen binding motifs disclosed herein. Aspects of the disclosure relate to a polynucleotide encoding a chimeric antigen receptor (CAR) or a T cell receptor (TCR) comprising one or more of the antigen binding motifs. Provided are antibodies and antigen binding systems that comprise a binding motif that binds CD20 and optionally a binding motif that binds CD19, and methods of producing and using the same. Antibodies and antigen binding systems of the present disclosure comprise CARs that comprise an anti-CD20 binding motif and an anti-CD19 binding motif. Provided are compositions, such as antibodies and CARs that are or comprise an anti-CD20 / anti-CD19 antigen binding system of the present disclosure, and cell therapies comprising the same, are useful, e.g., in the treatment of cancer.

MUC1 binding molecules are provided, including MUC1 single domain antibodies that specifically bind to the MUC1 extracellular region. The invention further relates to an anti-MUC1 single-domain antibody chimeric antigen receptor and application thereof, and particularly provides the chimeric antigen receptor, and an antigen binding domain of the chimeric antigen receptor comprises an MUC1 binding molecule containing the anti-MUC1 single-domain antibody. The immune cell containing the chimeric antigen receptor has a relatively high cell killing effect.