145 results about "CAR - Chimeric antigen receptor" patented technology

The present disclosure provides CD19 / CD20-binding domains and chimeric antigen receptors (CARs) based on the same, as well as corresponding nucleic acid molecules, vectors, cells, compositions, methods and uses, e.g., for the prevention and / or treatment of cancer and / or autoimmune disease.

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.

The present application relates to the technical field of biology and medicine, and particularly relates to a ULBP2 specific chimeric antigen receptor, a CAR-T cell and application thereof. The ULBP2 specific chimeric antigen receptor comprises a ULBP2 antigen binding domain, a transmembrane domain and an intracellular signaling domain, and the ULBP2 antigen binding domain comprises an amino acid sequence as shown in SEQ ID NO: 1. After the ULBP2 specific chimeric antigen receptor is transduced into lymphocytes, the killing ability of the lymphocytes on tumor cells is significantly enhanced, and the lymphocytes have a significant directional killing effect on tumor cells with high expression of ULBP2. The present application also relates to application of the ULBP2 specific CAR-T cell in combination with an anti-PD1 antibody for treating cancer.

The present invention provides for chimeric antigen receptor constructs capable of being expressed in dendritic cells (DCs), and DCs modified to express one or more chimeric antigen receptors (CARs) as well as compositions comprising these modified DCs and methods of stimulating an adaptive immune response in a subject. The intracellular domain of the CAR comprises a toll-interleukin receptor (TIL) intracellular signalling domain and a costimulating domain selected from CD3 signalling domain, CD28 signalling domain and a combined CD28 and CD3 signalling domain.

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.

Provided in the present invention is an isolated recombinant nucleic acid molecule, encoding a chimeric antigen receptor (CAR) polypeptide containing a single-chain antibody (scFv) targeting a B7-H3 polypeptide. Further provided are a recombinant vector containing the recombinant nucleic acid molecule, a recombinant T lymphocyte expressing the CAR polypeptide, a method for preparing the recombinant T lymphocyte, a drug for treating cancers that contains the recombinant nucleic acid molecule, recombinant vector, and recombinant T lymphocyte, and the use of the recombinant nucleic acid molecule, recombinant vector, and recombinant T lymphocyte in the treatment of cancers.

This invention provides a chimeric antigen receptor (CAR) targeting both BCMA and GPRC5D antigens and its uses. The chimeric antigen receptor (CAR) includes an extracellular localization signaling domain, an antigen domain targeting BCMA, an antigen domain targeting GPRC5D, a hinge region, a transmembrane region, a co-stimulatory factor, and an intracellular CD3ξ signaling domain. The antigen domain targeting BCMA includes a heavy chain variable region with an amino acid sequence as shown in SEQ ID NO: 1 and a light chain variable region with an amino acid sequence as shown in SEQ ID NO: 2. The antigen domain targeting GPRC5D includes a light chain variable region with an amino acid sequence as shown in SEQ ID NO: 3 and a heavy chain variable region with an amino acid sequence as shown in SEQ ID NO: 4. The dual chimeric antigen receptor, including an antigen domain targeting BCMA and an antigen domain targeting GPRC5D, can simultaneously recognize two anti-tumor targets, preventing tumor immune escape.

This invention discloses an engineered CAR-T cell targeting HIF-1α and its application in tumor immunotherapy. The CAR-T cell expresses a chimeric antigen receptor regulated by the hypoxia-responsive element HRE promoter, with its extracellular domain specifically binding to HIF-1α and its intracellular domain employing the 4-1BB+CD3ζ signaling module. Simultaneously, through immune checkpoint knockout and cytokine / chemokine modification, it achieves hypoxia-dependent activation, anti-exhaustion, high infiltration, and strong killing effects. The CAR-T cells of this invention significantly improve the adaptability to the solid tumor microenvironment and therapeutic efficacy, reduce off-target toxicity, and can be used to prepare drugs for treating malignant tumors such as lung cancer, liver cancer, pancreatic cancer, colorectal cancer, and glioblastoma, possessing significant clinical translational value.

Chimeric antigen receptors (CARs) that bind to Human Leukocyte Antigen (HLA)-pan DP, cells that comprise the CARS and methods of making and using the cells are provided.

The present application relates to a kind of based on logic gate double-target point chimeric antigen receptor modified TIL cell, lentivirus expression vector and application, belong to tumor immunotherapy and gene editing technical field.The TIL cell based on logic gate double-target point chimeric antigen receptor modified in the application, double-target point chimeric antigen receptor includes chimeric antigen receptor EGFR and chimeric antigen receptor GD2;Chimeric antigen receptor EGFR is composed of CD8 alpha signal peptide, anti-EGFR single-chain antibody, CD8 alpha transmembrane region, 4-1BB costimulatory domain and CD3 zeta intracellular signal domain in series;Chimeric antigen receptor GD2 is composed of CD8 alpha signal peptide, anti-GD2 single-chain antibody, CD28 transmembrane region, CD27 costimulatory domain and CD3 zeta intracellular signal domain in series.The present application solves the defects that lentivirus transduction targeting is poor in prior art, CAR signal activation specificity is insufficient, TIL cell is easily exhausted, has the advantages that gene integration is accurate, signal transduction is controllable, in-vivo survival time is long, can be efficiently used for the immunotherapy of double-antigen co-expression solid tumor.

Provided is a bispecific chimeric antigen receptor targeting CD19 and CD22, which comprises extracellular antigen binding domains of heavy-chain variable regions and light-chain variable regions of anti-CD19 and anti-CD22 antibodies. Further provided is a bispecific CAR-T cell targeting CD19 and CD22.

Provided are methods and compositions for obtaining functionally enhanced derivative effector cells obtained from the differentiation of genomically engineered iPSCs. The derivative cells provided herein have stable and functional genome editing that delivers improved or enhanced therapeutic effects. Also provided are therapeutic compositions and the use thereof comprising the functionally enhanced derivative effector cells alone, or with antibodies or checkpoint inhibitors in combination therapies.

This invention provides a chimeric antigen receptor comprising an NFIX-encoding gene, a self-cleaving peptide sequence F2A, and a CAR-encoding sequence. The NFIX-encoding gene is located upstream and is linked to the CAR-encoding sequence via the self-cleaving peptide sequence F2A. The sequence of the NFIX-encoding gene is shown in SEQ ID NO. 01, and the sequence of the self-cleaving peptide sequence F2A is shown in SEQ ID NO. 03. This invention also provides a chimeric antigen receptor T cell expressing the aforementioned chimeric antigen receptor. This invention further provides the application of the aforementioned chimeric antigen receptor or the aforementioned chimeric antigen receptor T cell in the preparation of drugs for treating cancer. This invention improves the antitumor therapeutic effect of CAR-T cells by introducing the NFIX expression element into engineered T cells, thereby enhancing their functional stability, proliferative capacity, and cytotoxic activity under continuous antigen stimulation.

Provided herein is a composition comprising, a cell, comprising nucleic acids encoding a chimeric antigen receptor (CAR) and one or more of signaling proteins selected from K13-vFLIP, MC159-vFLIP, cFLIP-L, cFLIP-p22, HTLV1-Tax and HTLV2-Tax, wherein the CAR comprises an a) extracellular antigen specific domain, b) a transmembrane domain and c) an intracellular signaling domain comprising an immunoreceptor tyrosine-based activation motif (ITAM); wherein c) is located at the C-terminus of the chimeric receptor. In some embodiments, the CAR further comprises one or more co-stimulatory domains. Also provided herein are methods for treating diseases using the compositions described herein. Further provided herein is a kinase inhibitor for use in therapeutic methods described herein.

The present invention relates to novel Chimeric Antigen Receptor (CAR) constructs, including CAR-T constructs, compositions for use with said constructs, and methods of treating patients with cancer and autoimmune diseases.

The present application provides humanized antibodies and antigen binding fragments thereof that bind to human poliovirus (PVR). The antibodies are useful in the treatment of tumors or cancers. The present application also provides a method of treating a cancer in an individual afflicted with a cancer comprising administering to the individual a therapeutically effective amount of chimeric antigen receptor (CAR) NK or T cells.

An mRNA composition for treating cancer is provided. The mRNA composition for treating cancer includes an mRNA encoding a CD47-targeted chimeric antigen receptor (CAR) and an mRNA encoding interleukin-12 (IL-12).

The present invention provides thymic T regulatory cells (ThyTreg cells) that encode or alternatively express a chimeric antigen receptor (CAR) comprising an extracellular domain, a hinge region, a transmembrane domain, and an intracellular domain, wherein the intracellular domain comprises a cytoplasmic costimulatory domain having a sequence having at least 85% identity with SEQ ID NO: 1, and a cytoplasmic stimulatory domain. The present invention also provides compositions and uses in immunotherapy.

This article provides a CD79b antibody and a CD79b-specific chimeric antigen receptor (CAR). Further, this article provides immune cells expressing the CD79b-specific CAR and a method for treating cancer by administering the CD79b-specific CAR immune cells.

The application belongs to the field of biological medicine, and relates to a lipid component of a chimeric antigen receptor neutrophil targeting Her2 generated in vivo, a preparation method thereof and application in solid tumor treatment. The lipid nanoparticle is a double-targeted lipid nanoparticle, and the double targeting is realized by Ly6G antibody fragments and NEBP polypeptides. The lipid nanoparticle comprises a lipid component and mRNA encoding Her2-CAR and IFN-gamma. The mRNA encoding Her2-CAR and IFN-gamma is delivered by the lipid nanoparticle LNP, and is delivered to neutrophils in vivo and expresses Her2-CAR and IFN-gamma to generate CAR-neutrophils, so that the cumbersome step of editing immune cells in vitro is omitted, and potential adverse reactions caused by reinfusion of CAR-immune cells prepared in vitro into the body are avoided.

Disclosed herein are engineered polyfunctional CD4+ T cells / CAR T cells and methods of their use for the treatment of cancers. One embodiment provides a method of producing polyfunctional CD4+ T cells by constitutively activating STAT5A in the cells to induce a polyfunctional phenotype. Also provided is a method of reversing exhaustion in tumor-specific CD4+ T cells by engineering the cells to express Fos, Jun, Nr4a1, or combinations thereof but not express Tox, Pdcd1, Ctla4, Haver2, Lag3, Tigit, Slam6, Nrf4a2, and administering the engineered cells to a subject.

Disclosed are compositions and methods for preventing graft versus host disease (GVHD) or allograft rejection in subjects receiving donor cells. Also disclosed are methods enhancing regulatory T (Treg) cells for use in preventing GVHD. Also disclosed are methods of suppressing alloreactive donor cells in a subject receiving transplant donor cells that involves adoptive transfer of the treated Treg cells. Also disclosed are enhanced Treg cells produced by the disclosed methods that have been engineered to express chimeric antigen receptor (CAR) polypeptide cells.

The present invention relates to the field of cell therapy. Disclosed are a fibroblast activation protein-targeting CAR T-cell, a preparation method therefor, and an application thereof. A CAR T-cell can be prepared by introducing an FAP-targeting chimeric antigen receptor (CAR) into a T lymphocyte, wherein the CAR in the CAR T-cell comprises a signal peptide, an antigen-binding domain, a hinge region, a transmembrane domain, a co-stimulatory signaling region, and a CD3 signaling domain. The CAR T-cell specifically recognizes the FAP by means of a single-chain variable fragment (scFv), which activates an intracellular signaling pathway, releasing cytokine IFN-γ, and exhibiting a cytotoxic effect on FAP+ cells, thereby achieving specific depletion of FAP+ cells at a lesion site. The CAR-T cell can be used for treating diseases characterized by upregulated FAP expression, such as fibrosis (pulmonary fibrosis, hepatic fibrosis, cardiac fibrosis, renal fibrosis, etc.), arthritis, autoimmune disorders (Crohn's disease, rheumatoid arthritis, etc.), and cardiovascular diseases, and demonstrates tremendous application potential and commercial value.

Antibodies that specifically bind to epidermal growth factor receptor variant III (EGFRvIII) and / or gene-amplified EGFR (e.g., humanized monoclonal antibodies and antigen-binding fragments), as well as conjugates and chimeric antigen receptors (CARs) containing such antibodies, are disclosed herein. Nucleic acid molecules encoding the antibodies, conjugates, or CARs disclosed herein, and host cells expressing the nucleic acid molecules are also provided. Methods for treating or detecting tumors, such as tumors expressing EGFRvIII and / or gene-amplified EGFR, using the disclosed compositions are further disclosed.

To provide new CAR designs comprising a modified CD3ζ chain, and cells including genetically modified immunoresponsive cells (e.g., T cells, NK cells, or CTL cells) comprising the CARs.SOLUTION: The present disclosure provides chimeric antigen receptors (CARs) that bind to an antigen of interest. The CARs can bind to a tumor antigen or a pathogen antigen. In certain non-limiting embodiments, the CAR comprises an extracellular antigen-binding domain, a transmembrane domain, and an intracellular signaling domain comprising a modified CD3ζ polypeptide.SELECTED DRAWING: Figure 1A

The present invention relates to an engineered cell comprising at least one chimeric antigen receptor (CAR) polypeptide and a switchable CAR in particular for use in the treatment of cancer, infectious disease or autoimmune disease, a pharmaceutical composition comprising the engineered cell and a kit comprising the engineered cell or at least two nucleic acids and / or vectors comprising a nucleotide sequence encoding the at least one CAR polypeptide or comprising a nucleotide sequence encoding the at least one switchable CAR polypeptide.

This invention provides a humanized antibody targeting CD19, a chimeric antigen receptor, and their uses. The humanized antibody comprises CD19VH and CD19VL, selected from groups 1) to 8). The chimeric antigen receptor targeting CD19 of this invention comprises an extracellular antigen recognition domain, a hinge region, a transmembrane region, and an intracellular domain targeting CD19. The extracellular antigen recognition domain targeting CD19 comprises CD19VH and CD19VL, selected from groups 1) to 8).

The invention is directed to a bispecific chimeric antigen receptor, comprising: (a) at least two antigen-specific targeting regions; (b) an extracellular spacer domain; (c) a transmembrane domain; (d) at least one co-stimulatory domain; and (e) an intracellular signaling domain, wherein each antigen-specific targeting region comprises an antigen-specific single chain Fv (scFv) fragment, and binds a different antigen, and wherein the bispecific chimeric antigen receptor is co-expressed with a therapeutic control. The invention also provides methods and uses of the bispecific chimeric antigen receptors.

The present application discloses immune effector cells expressing extracellular PD-L1 binding domain CAR and linking secretory interferon fusion protein and application methods thereof. The protein construct involved in the immune effector cells includes: (a) a chimeric antigen receptor (CAR) containing a PD-L1 binding domain; and (b) a secretory fusion protein containing IFN. The protein construct stimulates tumor cells to increase the expression amount or frequency of PD-L1, thereby further enhancing the killing ability of PD1-CAR-T cells on target cells and more effectively inhibiting or killing tumor cells.