874 results about "Chimeric antigen receptor" patented technology

This disclosure provides methods of increasing in vivo transfection efficiency and pharmacologic activity of T cells, by administering multiple small doses within a compact time period of T cell-targeted lipid nanoparticles encapsulating mRNA encoding an antigen receptor that recognizes an antigen of a cell against which immune activity is to be directed. Also provided are methods of depleting B cells, and methods of treating B cell-mediated diseases and disorders by depleting B cells and achieving immunological reset, entailing administration of immune cell-targeted lipid nanoparticles encapsulating mRNA encoding an antigen receptor recognizing a B cell marker as multiple small doses within a compact time period. The antigen receptor can be a T cell receptor or a chimeric antigen receptor.

Embodiments of the invention include compositions and methods related to engineered human mucosal-associated invariant T (eMAIT) cells for off-the-shelf use for clinical therapy for cancer, infectious, and autoimmune diseases. In some embodiments, the eMAIT cells are produced from healthy human donor peripheral blood, cord blood, or G-CSF mobilized peripheral blood. In particular embodiments, the eMAIT cells are produced from a pluripotent stem cell line and therefore can be of unlimited supply. In some embodiments, the eMAIT cells are engineered to express chimeric antigen receptors (CARs), or / and immune regulatory molecules, or / and allorejection resistance molecules. Embodiments of the invention also include compositions of matter comprising polynucleotides encoding mucosal-associated invariant T cell receptor alpha chain polypeptides and / or mucosal-associated invariant T cell receptor beta chain polypeptides.

The invention provides a GPRC5D single-domain antibody B11, and the GPRC5D single-domain antibody B11 has relatively strong binding activity and reaction specificity on GPRC5D. The invention provides an amino acid sequence of a single-domain antibody, an antibody derivative, a biological material and application thereof. The single-domain antibody provided by the invention can be used for constructing a chimeric antigen receptor T cell, and the chimeric antigen receptor T cell has stronger killing power on a target cell.

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 belongs to the technical field of gene therapy. Provided are a chimeric antigen receptor nanocomposite and a preparation method therefor and the use thereof in the preparation of an anti-aging drug. The provided chimeric antigen receptor nanocomposite comprises a chimeric antigen receptor DNA plasmid specifically recognizing senescent cells, a polymer coupled with a signal peptide, a free polymer and an antibody polymer targeting T cells, wherein the chimeric antigen receptor DNA plasmid, the polymer coupled with a signal peptide, the free polymer and the antibody polymer targeting T cells are sequentially mixed and incubated to form the chimeric antigen receptor nanocomposite. The chimeric antigen receptor nanocomposite can rapidly generate senescent cell-marked chimeric antigen T cells in vivo. The engineered T cells have the ability to specifically eliminate senescent cells in vivo, and can rapidly and durably eliminate senescent cells in vivo, which is irreplaceable and has wide application prospects.

Provided is a chimeric antigen receptor targeting GCC, comprising: an scFv that specifically recognizes GCC, a CD8 hinge region or a CD28 hinge region, a CD8 transmembrane region or a CD28 transmembrane region, a CD28 co-stimulatory signal domain or a 4-1BB co-stimulatory signal domain, and a CD3ζ signal domain; the scFv that specifically recognizes GCC comprises a heavy chain variable region VH and a light chain variable region VL, the VH comprising an HC CDR1 having the amino acid sequence shown in SEQ ID NO: 1, an HC CDR2 having the amino acid sequence shown in SEQ ID NO: 2, and an HC CDR3 having the amino acid sequence shown in SEQ ID NO: 3, and the VL comprising an LC CDR1 having the amino acid sequence shown in SEQ ID NO: 4, an LC CDR2 having the amino acid sequence shown in SEQ ID NO: 5, and an LC CDR3 having the amino acid sequence shown in SEQ ID NO: 6.

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.

The invention provides an antibody for specifically targeting GPRC5D, an application of the antibody, and a single-domain antibody F08 for specifically targeting GPRC5D, wherein the binding activity and the reaction specificity of the single-domain antibody F08 for the GPRC5D are relatively high. The invention also provides nucleic acid molecules encoding the single domain antibodies, vectors and recombinant host cells, as well as methods of producing the single domain antibodies and antibody derivatives. The single-domain antibody provided by the invention can be used for constructing a chimeric antigen receptor T cell, and the chimeric antigen receptor T cell has stronger killing power on a target cell.

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.

Provided herein are particles comprising polynucleotide constructs for generating cells expressing anti-CD22 chimeric antigen receptor, as well as vectors, such as lentiviral vectors, comprising same, cells comprising same, and methods of using same. Some embodiments include a surface-engineered lentiviral vector. In some embodiments, the lentiviral vector further encodes a synthetic receptor protein.

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.

The present disclosure provides bispecific chimeric antigen receptors targeting CD20 and BCMA. The CAR may comprise an scFv targeting CD20 and an scFv targeting BCMA, a hinge region, a transmembrane domain, a co-stimulatory region, and a cytoplasmic signaling domain. The chimeric antigen receptors can be used to treat autoimmune disorders or cancer.

Provided in the present invention are a single-domain antibody targeting TfR1 and the use thereof. Specifically, provided in the present invention are a corresponding anti-TfR1 antibody, a chimeric antigen receptor, a fusion protein, a recombinant protein and a coding nucleic acid thereof, an expression vector, a host cell, etc. In addition, an anti-TfR1 single-domain antibody-PMO conjugate is prepared. The single-domain antibody has properties such as binding activity and stability, and can be used for tumor therapy and immunodetection.

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.

The present disclosure provides bispecific chimeric antigen receptors targeting CD20 and BCMA. The CAR may comprise an scFv targeting CD20 and an scFv targeting BCMA, a hinge region, a transmembrane domain, a co-stimulatory region, and a cytoplasmic signaling domain. The chimeric antigen receptors can be used to treat autoimmune disorders or cancer.

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 present invention provides anti-Siglec-15 antibodies and antigen-binding fragments thereof as well as isolated nucleic acids, vectors, engineered cells, formulations thereof, and methods of use thereof for treating diseases including cancer and bone disease in a human subject. The invention is further directed to bispecific and multispecific antibodies, antibody-drug conjugates and chimeric antigen receptors derived from the anti-Siglec-15 antibodies and fragments thereof.

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 relates to the technical field of drug delivery, in particular to an ionizable lipid compound and application thereof. The invention provides an ionizable lipid compound simultaneously containing # imgabs0 # fragments. The chemical structure of the ionizable lipid compound is shown as a formula (I). The invention also provides an application of the ionizable lipid compound. The mRNA-LNP containing the ionizable lipid compound provided by the invention can integrally improve the biocompatibility of the LNP and the mRNA transfection efficiency, can efficiently deliver a chimeric antigen receptor (CAR) to cells which are extremely difficult to transfect, such as T cells, NK cells, macrophages and the like, especially when being applied to the field of cell therapy, and has an unexpected technical effect.

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.

Intracellular delivery of a genetic construct to immune cells including: obtaining a deterministic mechanoporation (DMP) platform that includes a substrate having a surface and a plurality of capture sites, each said capture site having a boundary shape at the surface adapted and configured to support thereon a cell, and each said capture site having a bottom and including a sub-micron-scale projection extending from the bottom toward the surface of the substrate, wherein said projection is adapted and configured to penetrate a cell membrane and / or wall of the cell, and wherein the substrate has a plurality of aspiration vias situated at the bottom of the capture sites; introducing the cells to the surface in a liquid media; capturing the cells within the capture sites by applying a first hydrodynamic force; applying a second hydrodynamic force on the captured cell and locally rupturing the membrane and / or wall of the cell with the projection, introducing the genetic construct into the cells, and releasing the porated cells from the capture sites. Also disclosed are methods of chimeric antigen receptor (CAR) T cell adoptive immunotherapy and T cell receptor (TCR) therapy.

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.

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 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.