1687 results about "Chimeric antigen receptor" patented technology

The invention provides compositions and methods for treating cancer by using immune effector cells (e.g., T cells, NK cells) engineered to conditionally express an agent which enhances the immune effector response of an immune effector cell that expresses a Chimeric Antigen Receptor (CAR). The conditional agents described herein include agents that target a cancer associated antigen, e.g., a CAR, agents that inhibit one or more checkpoint inhibitors of the immune response, and a cytokine.

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.

Various embodiments of the invention provide binding molecules for B-lymphocyte antigen (e.g., CD 19 and CD20), including antigen recognizing receptors (e.g., CARs) that target B-lymphocyte antigens (e.g., CD 19 and CD20). Embodiments of the invention also provide cells expressing such binding molecules, therapeutics compositions comprising such cells, and methods for treating diseases or disorders associated with B-lymphocyte antigen (e.g., CD19 and CD20), including a hematologic cancer, an autoimmune disease (e.g., multiple sclerosis and systemic lupus erythematosus).

Disclosed herein are compositions comprising allogeneic, low immunogenic chimeric antigen receptor (CAR)-targeting biomimetic nanovesicles (BioNVs), and methods of treating, preventing, and / or ameliorating cancer using the same.

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.

Disclosed are lipid nanoparticle (LNP) delivery systems that specifically target T cells. The LNP delivery system comprises antibodies conjugated to the surface of the LNP, e.g., via maleimide chemistry, that target at least two T cell surface proteins, e.g., CD3 and CD28. The LNP delivery system can have a single population of LNP conjugated to either a bispecific antiCD3 / antiCD28 antibody, or two monospecific antiCD3 and antiCD28 antibodies, or two populations of LNP wherein each population comprises a monospecific antibody. The payload of the LNP delivery system can be, e.g., mRNA encoding chimeric antigen receptors (CAR), a linear DNA fragment or a plasmid encoding chimeric antigen receptors (CAR) or therapeutic proteins such as antibodies, components of a gene editing systems (e.g., CRISPR-Cas), small molecules, antibody-drug conjugates (ADC), and any combination thereof, either encapsulated in the LNP or attached to its surface (e.g., conjugated). Also provided are lipids, pharmaceutical compositions, kits, and methods of treatment.

The present invention discloses a nano antibody against BCMA and its preparation method and application, and relates to the field of biomedical technology. The present invention uses CRISPR / Cas9 technology to knock out B2M and TRAC genes in T cells to prepare universal CAR-T cells; the nano antibody targeting BCMA and the natural ligand SIRPα extracellular N-terminal V region of CD47, the transmembrane region of CD28, the intracellular signal region of 4-1BB and the intracellular signal region of CD3ζ are connected in series to form a dual-targeted chimeric antigen receptor for the treatment of multiple myeloma, so as to solve the high recurrence problem faced by CAR-T cell therapy in the treatment of multiple myeloma. The universal CAR-T cells prepared by the present invention have strong killing activity against multiple myeloma cells, effectively improve the treatment effect, and provide a key material for the subsequent development of adoptive immunotherapy with high efficiency and lasting anti-tumor activity.

The invention relates to a method for evaluating the specific killing ability of engineered natural killer cells. Specifically, the invention provides a method for dynamically detecting the killing ability of the immune effector cell in real time, a target cell capable of stably expressing fluorescent protein is constructed, and the real-time killing of the immune effector cell on the target cell is accurately reflected through the disappearance condition of a fluorescence signal of the target cell. In the system provided by the invention, target cells can be added again for continuous challenge, tumor invasion is simulated, and the in-vitro killing function of the natural killer cells of the chimeric antigen receptor is comprehensively evaluated. The method provided by the invention provides effective and accurate evaluation for process development of immune effector cells, especially engineered and modified NK cell products, and provides effective analysis support for researching immune curative effects of NK cells and the like.

A CD19-OR-CD20 chimeric antigen receptor (CAR) protein construct is provided. Also provided are nucleic acids encoding the CD19-OR-CD20 CAR; and methods of use, e.g. in the treatment of B cell malignancies. The CD19-OR-CD20 CAR of the invention is a bispecific CAR that can trigger T-cell activation upon detection of either CD19 or CD20 (or both). It is a single molecule that confers two-input recognition capability upon human T cells engineered to stably express this CAR.

A CD20-OR-CD19 chimeric antigen receptor (CAR) protein construct is provided. Also provided are nucleic acids encoding the CD20-OR-CD19 CAR; and methods of use, e.g. in the treatment of B cell malignancies. The CD20-OR-CD19 CAR of the invention is a bispecific CAR that can trigger T-cell activation upon detection of either CD19 or CD20 (or both). It is a single molecule that confers two-input recognition capability upon human T cells engineered to stably express this CAR.

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.

Provided herein are compositions and methods for adoptive cell therapy comprising engineered immune cells that express a tumor antigen-targeted chimeric antigen receptor and a prodrug converting enzyme.

The invention discloses a Trop2 targeting chimeric antigen receptor macrophage as well as a preparation method and application thereof. The macrophage contains a specific CAR (chimeric antigen receptor) targeting Trop2 and a blocking agent for blocking an immunosuppression signal; the amino acid sequence of the Trop2 specific CAR targeting the breast cancer is as shown in SEQ ID NO. 1; the nucleotide sequence of the mRNA of the specific CAR of the targeted Trop2 is as shown in SEQ ID NO. 2. According to the invention, LNP is adopted to co-deliver CAR mRNA and TLR agonists, and macrophages are edited in vivo to generate CAR-macrophages expressing Trop2 in situ, so that a tedious engineering cell in-vitro preparation process is omitted, and potential whole-body toxic and side effects caused by immune cell system reinfusion are avoided.

The invention discloses preparation and application of a targeting LYPD3 chimeric antigen receptor T cell. The chimeric antigen receptor comprises an LYPD3 antigen binding domain, a transmembrane domain, a costimulatory signal transduction domain and an intracellular signal transduction domain, the LYPD3 antigen binding domain comprises a heavy chain variable region with CDR-H1, CDR-H2 and CDR-H3 and a light chain variable region with CDR-L1, CDR-L2 and CDR-L3, and the CDR-H1, the CDR-H2 and the CDR-H3 are respectively composed of amino acid sequences of SEQ ID NO: 3, SEQ ID NO: 4 and SEQ ID NO: 5. And the CDR-L1, the CDR-L2 and the CDR-L3 are respectively composed of amino acid sequences as shown in SEQ ID NO: 6, SEQ ID NO: 7 and SEQ ID NO: 8.

The invention provides a CAR-NK cell for knocking out KIR2DL5 targeting HER2 as well as a preparation method and application of the CAR-NK cell, and belongs to the technical field of genetic engineering.The CAR-NK cell is obtained by adopting a chimeric antigen receptor with HER2 as a target spot to infect an NK cell and then knocking out a KIR2DL5 gene; the chimeric antigen receptor taking the HER2 as the target spot comprises an HER2 single-chain antibody; the nucleic acid artificial sequence of the HER2 single-chain antibody is as shown in SEQ ID NO. 2. According to the application disclosed by the invention, the interaction of KIR2DL5-PVR is blocked by knocking out NK cell immune checkpoints, so that tumor immune escape is avoided, and the activity of killing tumor cells by CAR-NK cells is remarkably enhanced; according to the invention, by optimizing the nucleic acid artificial sequence of HER2, the secretion ability of CAR-NK cell factors, the tumor killing efficiency and the in-vivo inhibition effect on tumors can be improved.

In one embodiment, the present disclosure provides an engineered cell having a first chimeric antigen receptor polypeptide including a first antigen recognition domain, a first signal peptide, a first hinge region, a first transmembrane domain, a first co-stimulatory domain, and a first signaling domain; and a second chimeric antigen receptor polypeptide including a second antigen recognition domain, a second signal peptide, a second hinge region, a second transmembrane domain, a second co-stimulatory domain, and a second signaling domain; wherein the first antigen recognition domain is different than the second antigen recognition domain.

Provided are single domain antibodies having binding specificity to the human GPRC5D protein. Such antibodies, as well as their multi-specific counterparts and chimeric antigen receptors are capable of targeting cancer cells expressing GPRC5D, and thus can be used to treat the cancer, in particular hematological cancers.

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.

The invention discloses construction and application of a targeted exosome chimeric antigen receptor molecule for treating HIV (human immunodeficiency virus) infection, and belongs to the technical field of biological medicines. According to the invention, the mRNA for coding the anti-HIV CAR is directionally packaged into the targeting exosome. Nanometer antibody sequences of CD3, CD4 and CD8 < + > T receptors on targeted T cells are fused to the N terminal of LAMP-2B to construct a specific targeting plasmid, so that targeting peptides are expressed on the surface of an exosome membrane, expression plasmids containing RNA binding protein L7A and exosome tag protein CD63 are constructed, and HEK293F cells are co-transfected by the expression plasmids and CAR plasmids containing C / D box to obtain the exosome loaded with CAR mRNA and targeted to the T cells. When the exosome is incubated with PBMC (peripheral blood mononuclear cells) in vitro or is transfused back into a humanized mouse body, human CAR-T cells can be constructed, and the exosome has remarkable activity of killing virus infected cells.

As described below, the present disclosure features polypeptides capable of binding a cluster of differentiation 5 (CD5) antigen and polynucleotides encoding said CD5-binding polypeptides, compositions comprising the same, and methods for use thereof. The disclosure also features lipid nanoparticles comprising the CD5-binding polypeptides and methods for use thereof for delivery of a polynucleotide (e.g., a polynucleotide encoding a chimeric antigen receptor) to a T cell in vivo.

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.

The present invention relates to a bispecific chimeric antigen receptor targeting CD117 and CD7 and its application, wherein the bispecific chimeric antigen receptor comprises a signal peptide, an antigen binding domain, a hinge region, a transmembrane domain and a signal transduction domain, wherein the antigen binding domain comprises a CD117 binding domain and a CD7 binding domain. The bispecific chimeric antigen receptor provided by the present invention combines targeted antibodies for CD117 and CD7 together, recognizes and binds to two different antigens at the same time, enhances the targeted elimination ability of malignant cells, and by acting on hematopoietic stem cells and immune cells at the same time, can more effectively eliminate tumor cells in the receptor, while retaining or reconstructing normal hematopoietic and immune functions.

The present invention relates to chimeric antigen receptors (CAR) containing TCR hinge and transmembrane domains. The present invention also relates to using transmembrane pairing to enhance the stability and specificity of dual antigen CARs. The present invention also relates to new CARs containing transmembrane and signaling domains from cytokine receptors.

The invention provides an anti-FAP nano antibody. The anti-FAP nano antibody comprises a complementary determining region (CDR) and a framework region (FR), wherein the complementarity determining region CDR comprises complementarity determining regions CDR1-CDR3, and the complementarity determining regions CDR1-CDR3 are And the framework area FR comprises framework areas FR1-FR28. According to the invention, an alpaca phage antibody library immunized by human FAP extracellular domain protein is successfully constructed, seven new anti-FAP nano antibody VHH sequences are screened from the alpaca phage antibody library, and the nano antibody sequences not only can recognize human FAP antigens, but also can recognize mouse FAP antigens. Meanwhile, the nano antibody sequence can be prepared into chimeric antigen receptor T cells (CAR-T) and can effectively kill cells highly expressing human or mouse FAP, so that the nano antibody sequence has an immunotherapy prospect of being applied to targeted FAP positive cells including tumor and fibrosis diseases.

Provided herein are compositions and methods for adoptive cell therapy comprising engineered immune cells that express a tumor antigen-targeted chimeric antigen receptor and a prodrug converting enzyme.

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.

This invention relates to modified T cells that inducibly express a bioactive molecule, such as IL-7, and constitutively expresses an antigen receptor, such as a T cell receptor or chimeric antigen receptor that binds to a tumour antigen. The modified T cells may comprise a nucleic acid construct that comprises a first nucleotide sequence encoding the bioactive molecule, a second nucleotide sequence encoding the antigen receptor; an inducible promoter operably linked to the first nucleotide sequence and a constitutive promoter operably linked to the second nucleotide. Nucleic acid constructs and vectors are provided, as well as T cells comprising such constructs and vectors and therapeutic methods and uses thereof.

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.