476 results about "Transmembrane Region" patented technology

The present invention belongs to the fields of molecular biology and immunology and relates to a chimeric antigen receptor combining EGFR (epidermal growth factor receptor) family proteins and a composition and uses thereof The present invention particularly relates to the chimeric antigen receptor comprising polypeptides efficiently combining the EGFR family proteins and transmembrane domains, wherein the polypeptides efficiently combining EGFR family proteins comprise HERIN. The chimeric antigen receptor can promote the proliferation ability and killing effect of T cell at the premise of maintaining the killing specificity of the T cell.

A redirected Treg cell is endowed with specificity toward a selected target antigen or ligand. The cell contains a chimeric receptor polypeptide that is expressed in a single, continuous chain, with an extracellular recognition region displayed on the surface of the cell, a transmembrane region and an intracellular signaling region. The extracellular recognition region is specific for the selected target antigen or ligand. The intracellular signaling region includes a combination of T-cell signaling polypeptide moieties, which combination, upon binding of the extracellular recognition region to the selected target antigen or ligand, triggers activation of the redirected Treg cells to cause suppression of T-cell mediated immunity. Such redirected Treg cells may be used to suppress undesired activity of T effector cells thereby mediating an immune or inflammatory response. They are particularly useful in treating T effector cell-mediated diseases, such as inflammatory bowel disease, transplant rejection and GVH disease.

The invention relates to a chimeric antigen receptor of a targeted GPC3 (Glypican 3) and an application thereof. Specifically, the invention provides a polynucleotide sequence, wherein the polynucleotide sequence is selected from: polynucleotide sequences (1) containing a coding sequence of a CD8 antigen leading peptide, a coding sequence of an anti-GPC3 single-chain antibody, a coding sequence of a human CD8 alpha hinge region, a coding sequence of a human CD8 transmembrane region, a coding sequence of a human 41BB intracellular region, and a coding sequence of a human CD3 zeta intracellular region, and a coding sequence of an optional fragment of an EGFR (Epidermal Growth Factor Receptor) sequence containing an extracellular domain III and an extracellular domain IV, wherein the coding sequences are sequentially connected; and complementary sequences (2) of the polynucleotide sequences (1). The invention provides a CAR (chimeric antigen receptor) coded by the polynucleotide sequences and a T cell expressing the CAR. The prepared CAR-T cell has a function of strongly killing a specific tumor cell, and the kill effectiveness is more than 90% under the condition that the effector-target ratio is 20:1.

The invention belongs to the technical field of biology and new medicines and discloses a chimeric antigen receptor (CAR) iRGD-scFv (G250)-CD8-CD28-CD137-CD3zeta and application thereof. The chimeric antigen receptor is formed by series connection of tumor penetrating peptide iRGD, a single-chain antibody of a humanized anti-human renal carcinoma antigen G250, a hinge region and a transmembrane region of CD8, and intracellular signal structural domains of CD28, CD137 and CD3zeta. The chimeric antigen receptor can be used for modifying T lymphocytes, and the modified T lymphocytes can be used for renal carcinoma treatment.

The invention provides a BCMA-based (B cell maturation antigen-based) chimeric antigen receptor, comprising following cis-form cascade domains: CD8a leader region, scFv fragment BCMA scFv of anti-BCMA antibody, CD8a hinge region and transmembrane region, CD28 intracellular signal domain and CD3 Zeta intracellular signal domain; the CD3 Zeta intracellular signal domain is wild CD3 Zetaintracellular signal domain or mutant CD3 Zeta mut intracellular signal domain; the BCMA-based chimeric antigen receptor can enhance anti-apoptotic capability of T-cells and enhance CAR T-cell and antigen bonding and signal conduction; T-cells with the BCMA-based chimeric antigen receptor show good tumor targeting performance in in-vivo experiments, tumors diminish significantly after two weeks of dosage, and the T-cells have excellent therapeutic effect in vivo.

The invention relates to a double-target CD19 and CD22 chimeric antigen receptor and application thereof, in particular to a polynucleotide sequence which is selected from (1) a coding sequence comprising anti-CD22 and anti-CD19 single-chain antibodies which are connected sequentially, a coding sequence of a human CD8 hinge region, a coding sequence of human CD8 transmembrane region, a coding sequence of a human 41BB intracellular region, a coding sequence of a human CD3 zeta intracellular region and a polynucleotide sequence of a coding sequence of a fragment, comprising an extracellular domain III and a extracellular domain IV, of an optional EGFR; and (2) a complementary sequence of the (1) polynucleotide sequence. The invention further provides a relevant fusion protein, a carrier comprising the coding sequence and application of the fusion protein, the coding sequence and the carrier. The prepared CD19-CD22-BBzCAR-T cell has a strong killing function to the specific tumor cell, CD107a expression and IFN gamma secretion are high, and the killing efficiency to the target cell can reach about 80% under the situation that the effector-target ratio is 10:1.

The invention provides a CD19 targeted CAR (chimeric antigen receptor)-T cell, a preparation method and an application and relates to the field of immune cells. The activation capacity of T cells in CAR-T cell therapy can be improved, the problem of insufficient transfection efficiency can be solved, and the CAR-T cell has a high killing capacity for CD19. The CD19 targeted CAR-T cell expresses a CD19 targeted CAR gene on surface, and the CD19 targeted CAR gene is formed by connecting a single-chain antibody CD19ScFv of CD19, a hinge region and a transmembrane region of CD8, an intracellular signal structure of CD28, an intracellular signal structure of 4-1BB and an intracellular signal structural domain of CD3zeta in series, and the base sequence of the CD19 targeted CAR gene is shown as SEQ ID NO:2.

The invention relates to a chimeric antigen acceptor of a target BCMA (B cell maturation antigen). The chimeric antigen acceptor comprises an extracellular identification region, a hinge region, a transmembrane region and an intracellular signal region, wherein the extracellular identification region has a BCMA resisting nanometer antibody sequence, and the BCMA resisting nanometer antibody sequence is a heavy-chain variable region sequence combining with BCMA and from alpacas. More specifically, the BCMA resisting nanometer antibody sequence is BCMA monoclonal antibody B1 or B65, the amino acid sequence of the B1 is as shown in SEQID NO.1, and the amino acid sequence of the B65 is as shown in SEQID NO.2. According to the chimeric antigen acceptor disclosed by the invention, compared witha traditional mouse-derived SCFV or humanized SCFV, the nanometer antibody from the alpacas is used, and has small molecule quantity and immunogenicity, the possibility that CAR-T cells prepared on the base of the nanometer antibody produce HAMA effects in vivo is smaller, the remaining time of the CAR-T cells in vivo can be longer, the CAR-T cells pass through BCMA protein on the surfaces of target tumor cells and activate signal channels at the downstream part of T cells, the capacity for killing tumor cells having BCMA target points is given to the T cells, and BCMA positive blood tumor canbe efficiently and specifically treated.

The invention belongs to the field of genetic engineering, and concretely relates to a BCMA-targeting chimeric antigen receptor and an application thereof. The chimeric antigen receptor comprises an antigen recognition region, a hinge region, a transmembrane region and an intracellular signal domain; and the amino acid sequence of an extracellular recognition region is represented by SEQ ID NO.1 or SEQ ID NO.2 or SEQ ID NO.3. The chimeric antigen receptor can effectively remove BCMA-expressing tumor target cells after being expressed in immune cells, has no toxic or side effects on antigen-negative cells, and can be used for the targeted therapy of tumors.

The invention belongs to the field of genetic engineering and particularly relates to an anti-CD123 single-chain antibody, a chimeric antigen receptor combined by the same, and application thereof. The anti-CD123 single-chain antibody is a CD123 antigen-recognizing peptide with an amino acid sequence shown as SEQ ID NO: 1. The anti-CD123 antigen chimeric antigen receptor is formed by sequentiallyconnecting the CD123 antigen-recognizing peptide (ScFv), a hinge region, a transmembrane region and an intracellular signal region. When being expressed in immune cells, the anti-CD123 antigen chimeric antigen receptor can not only effectively eliminate target tumor cells, which can express CD123 antigens, without toxicity to tumor cell with negative antigens/incapable of expressing CD123, but also maintain the positive rate of a CD123-targeted antigen chimeric antigen receptor (CAR) during patient cell culturing, which can propagate for a long time after being stimulated by target antigens and accordingly achieves targeted treatment on tumors.

The invention relates to the field of tumor cellular immunotherapy, and in particular relates to a recombinant lentivirus and application thereof. The recombinant lentivirus comprises a chimeric antigen receptor, wherein the chimeric antigen receptor mainly comprises signal peptide, an antigen recognition domain, a transmembrane domain, an intracellular co-stimulation signal transduction domain and a CD3 zeta signal transduction domain which are serially connected; the intracellular co-stimulation signal transduction domain mainly comprises a human TLR2 (Toll Like Receptor 2) intracellular domain. A GPC3 CAT T (Glypican 3 CAT T) cell prepared from the recombinant lentivirus has an intense cell killing effect on liver cancer cells, a Th1 cell factor can be highly expressed, a tumor killing effect caused by non-CAR T (Chimeric Antigen Receptor T) cell can be stimulated to the maximum extent, escape and potential reoccurrence risk of GPC 3-tumor cells can be effectively prevented, the tumor cells can be killed by T cells expressing the chimeric antigen receptor, normal tissue can be slightly damaged, a tumor immunosuppression micro environment can be broken through, and thus a relatively good treatment effect on solid tumor can be achieved.

An expression cassette, wherein said expression cassette comprises: (a) an ie 1 promoter from white spot syndrome virus or a variant thereof; (b) a nucleic acid sequence encoding an N-terminal gp64 signal peptide or variant thereof, a nucleic acid sequence encoding an antigenic peptide, a nucleic acid encoding a transmembrane region, and a nucleic acid encoding a gp64 cytoplasmic region or variant thereof; in which the promoter is operably linked to the nucleic acid sequence.

The invention provides an OCTS-CAR technique-based OCTS-CAR double-targeting chimeric antigen receptor, a coding gene and a recombinant expression vector and establishment and application of the OCTS-CAR double-targeting chimeric antigen receptor, the coding gene and the recombinant expression vector. The OCTS-CAR double-targeting chimeric antigen receptor includes a CD8 leader membrane receptor signal peptide, a double-antigen binding region, a CD8 Hinge chimeric receptor gemel, a CD8 transmembrane chimeric receptor transmembrane region, a CD28 chimeric receptor co-stimulatory factor, a CD134 chimeric receptor co-stimulatory factor and a TCR chimeric receptor T cell activating domain which are connected sequentially and in series, wherein the double-antigen binding region comprises heavy-chain VH and light-chain VL, connected in a certain mode, of two single-chain antibodies, an antibody Inner-Linker and an Inter-Linker between single-chain antibodies, and the two single-chain antibodies are formed by combining any two of a BCMA single-chain antibody, a CD319 single-chain antibody, a CD38 single-chain antibody, a PDL1 single-chain antibody and a CD123 single-chain antibody; in addition, the invention further provides a gene encoding the OCTS-CAR double-targeting chimeric antigen receptor, the recombinant expression vector and an establishment method and application of the gene encoding the OCTS-CAR double-targeting chimeric antigen receptor and the recombinant expression vector.

The invention discloses an ROR1 specific chimeric antigen receptor and an application thereof. The ROR1 specific chimeric antigen receptor is a protein formed through serially connecting scFv of anti-human ROR1, the hinge region and the transmembrane region of CD8alpha, the transmembrane region and the intracellular region of CD28 and the intracellular region of CD3zeta from the amino end to the carboxyl end. T cells modified with the chimeric antigen receptor have a specific killing effect on tumor cells, and are expected to be in widely used in treatment of all kinds of solid tumor and blood tumors.

The invention belongs to the field of gene engineering, and particularly relates to a chimeric antigen receptor for identifying carcino-embryonic antigens and an application of the chimeric antigen receptor. A single-chain fragment variable (scFV) for identifying the carcino-embryonic antigens, a hinge region, a transmembrane region and an intracellular signal domain are sequentially connected to form the chimeric antigen receptor, and the amino acid sequence of the single-chain fragment variable (scFV) for identifying the carcino-embryonic antigens includes M5A-scFV amino acid sequence or amino acid sequence acquired by performing random mutation on M5A-scFV polypeptide. When the chimeric antigen receptor identifies the carcino-embryonic antigens, T lymphocytes can be more stably expressed, the positive rate of a chimeric antigen receptor of a target CEA (carcino-embryonic antigen) can be maintained in the culture process of patient cells, proliferation capacity and tumor killing capacity of CAR-T (chimeric antigen receptor T lymphocytes) can be improved, the chimeric antigen receptor does not have toxic and side effects on confrontation of original negative cells, can be used for targeted treatment of tumors and high in humanization degree, immunogenicity of the CAR can be effectively reduced, and continuity and safety of the CAR-T in human bodies are improved.