477 results about "Transmembrane Region" patented technology

The invention relates to nucleic acids encoding a synthetic transmembrane region as well as to membrane associated proteins containing these synthetic transmembrane regions. The design of the synthetic transmembrane region allows various properties of a protein, such as its level of expression, and relative response to ligand binding to be tailored as required for a specific purpose.

The present invention relates to chimeric transmembrane immunoreceptors, named “zetakines,” comprised of an extracellular domain comprising a soluble receptor ligand linked to a support region capable of tethering the extracellular domain to a cell surface, a transmembrane region and an intracellular signaling domain. Zetakines, when expressed on the surface of T lymphocytes, direct T cell activity to those specific cells expressing a receptor for which the soluble receptor ligand is specific. Zetakine chimeric immunoreceptors represent a novel extension of antibody-based immunoreceptors for redirecting the antigen specificity of T cells, with application to treatment of a variety of cancers, particularly via the autocrin / paracrine cytokine systems utilized by human maligancy. In a preferred embodiment is a glioma-specific immunoreceptor comprising the extracellular targeting domain of the IL-13Rα2-specific IL-13 mutant IL-13(E13Y) linked to the Fc region of IgG, the transmembrane domain of human CD4, and the human CD3 zeta chain.

The invention discloses a chimeric antigen receptor hCD19scFv-CD8a-CD-28-CD3zata and application thereof. The chimeric antigen receptor is serially connected by an anti-human CD19 monoclonal antibody H119a light chain and heavy chain variable region (hCD19scFv), human CD8a hinge region, a human CD28 transmembrane region, an intracellular region and a human CD3zata intracellular region. The chimeric antigen receptor is used for modifying T lymphocyte, and the modified T lymphocyte (CAR-T cell) can be used for treating the tumor with positive surface CD19.

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.

The present invention relates to chimeric transmembrane immunoreceptors, named “zetakines,” comprised of an extracellular domain comprising a soluble receptor ligand linked to a support region capable of tethering the extracellular domain to a cell surface, a transmembrane region and an intracellular signalling domain. Zetakines, when expressed on the surface of T lymphocytes, direct T cell activity to those specific cells expressing a receptor for which the soluble receptor ligand is specific. Zetakine chimeric immunoreceptors represent a novel extension of antibody-based immunoreceptors for redirecting the antigen specificity of T cells, with application to treatment of a variety of cancers, particularly via the autocrin / paracrine cytokine systems utilized by human malignancy. In a preferred embodiment is a glioma-specific immunoreceptor comprising the extracellular targetting domain of the IL-13Rα2-specific IL-13 mutant IL-13(E13Y) linked to the Fc region of IgG, the transmembrane domain of human CD4, and the human CD3 zeta chain.

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 discloses an anti-BCMA chimeric antigen receptor, an encoding gene, a recombinant expression vector and an establishing method and application of the anti-BCMA chimeric antigen receptor, the encoding gene and the recombinant expression vector. The receptor comprises a CD8 leader chimeric receptor signal peptide, a BCMA single-chain antibody heavy chain VH, an Optimal Linker C, a BCMA single-chain antibody light chain VL, a CD8 Hinge chimeric receptor hinge, a CD8 Transmembrane chimeric receptor transmembrane domain, a CD137 chimeric receptor co-stimulatory factor and a TCR chimeric receptor T cell activating domain which are sequentially connected in series. In addition, the invention further discloses the encoding gene and the recombinant expression vector of the anti-BCMA chimeric antigen receptor and the establishing method and application of the encoding gene and the recombinant expression vector. The secretion of cell factors and the cytotoxicity in vitro of CAR-T cells can be remarkably improved, and the clinical treatment effect is outstanding.

The present invention discloses a chimeric antigen receptor, a gene and a recombinant expression vector thereof, an engineered CD19 targeting NKT cell and applications thereof. The chimeric antigen receptor is CD19ScFv-CD8-CD137-CD3 zeta, and consists of a hinge region and a transmembrane region of the CD19ScFv and CD8, an intracellular signal structural domain of CD137, and an intracellular signal structural domain of CD3 zeta, and the the hinge region, the transmembrane region, the intracellular signal structural domain of CD137 and the intracellular signal structural domain of CD3 zeta are connected in series. When used to treat advanced stage CD19-positive B-cell acute lymphocytic leukemia, the NKT cell modified by the chimeric antigen receptor CD19ScFv-CD8-CD137-CD3 zeta provided by the present invention has good specific killing activity on leukemic cells, and has certain therapeutic effect on advanced stage CD19-positive B-cell acute lymphocytic leukemia patients who are repeatedly subjected to therapy such as radiotherapy, chemotherapy and symptomatic therapy by other drugs but cannot recover obviously.

The present invention relates to chimeric transmembrane immunoreceptors, named “zetakines,” comprised of an extracellular domain comprising a soluble receptor ligand linked to a support region capable of tethering the extracellular domain to a cell surface, a transmembrane region and an intracellular signalling domain. Zetakines, when expressed on the surface of T lymphocytes, direct T cell activity to those specific cells expressing a receptor for which the soluble receptor ligand is specific. Zetakine chimeric immunoreceptors represent a novel extension of antibody-based immunoreceptors for redirecting the antigen specificity of T cells, with application to treatment of a variety of cancers, particularly via the autocrin / paracrine cytokine systems utilized by human maligancy. In a preferred embodiment is a glioma-specific immunoreceptor comprising the extracellular targetting domain of the IL-13Rα2-specific IL-13 mutant IL-13(E13Y) linked to the Fc region of IgG, the transmembrane domain of human CD4, and the human CD3 zeta chain.

The invention belongs to the field of gene engineering, and relates to chimeric antigen receptor of anti-human CD19 antigen and application thereof. The chimeric antigen receptor of anti-human CD19 antigen comprises polypeptide (scFv) for recognizing human CD19 antigen, a hinge region, a transmembrane region and an intracellular signal domain which are connected in sequence, wherein an amino acid sequence of the polypeptide (scFv) for recognizing human CD19 antigen is as shown in SEQ ID NO.1, SEQ ID NO.2, SEQ ID NO.3 or SEQ ID NO.4. The chimeric antigen receptor can be more stably expressed in T lymphocyte, has the capacity for properly removing cancer cell, can not only maintain the positive rate of CD19 targeted chimeric antigen receptor during the cell culture of a patient, but also enhance the capacity for CAR-T multiplication and tumor killing, does not have toxic and / or side effects on antigen-negative cell, and can be applied to the targeted therapy of tumor.

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 single chimeric converter for a T-cell signal and application thereof, which belongs to the fields of molecular biology and immunology. Specifically speaking, the single chimeric converter is formed by connection of a polypeptide highly efficiently bonding with immunosuppression molecules on the surfaces of tumor cells and / or tumor matrix cells to a transmembrane domain originated from a high-affinity receptor and an intracellular peptide fragment of a costimulatory signal molecule through a hinge structure. Out-membrane polypeptide receives a signal of the immunosuppression molecules on the surfaces of tumor cells and / or tumor matrix cells and transmits the signal into a cell, a second signal of immune cells is activated through the intracellular peptide fragment of the costimulatory signal molecule, so multiplication capacity of the immune cells and the secretion function of cell factors are enhanced, and the survival time of the activated immune cells is prolonged; thus, side-effects of a tumor immunosuppression microenvironment on adoptive cell therapy effector cells are overcome.

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 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.

The invention relates to a chimeric antigen receptor targeting to CD19-41BB-tEGFR, and application thereof. Specifically, the invention provides a polynucleotide sequence. The polynucleotide sequenceis selected from (1) a polynucleotide sequence containing, successively connected, a coding sequence of an anti-CD19 single-chain antibody, a coding sequence of the hinge region of human CD8alpha, a coding sequence of the transmembrane region of human CD8, a coding sequence of the intracellular region of human 41BB, a coding sequence of the hinge region of human CD8zeta and an optional coding sequence of an EGFR fragment containing an extracellular domain III and an extracellular domain IV; and (2) complementary sequences of the polynucleotide sequence described in (1). The invention also provides related fusion proteins, vectors containing the coding sequences, and application of the fusion proteins, the coding sequences and the vectors.

The invention provides a PSCA (prostate stem cell antigen) and PD-L1 targeted CAR based on OCTS (one CAR with two ScFvs)-CAR (chimeric antigen receptor), an encoding gene, an OCTS-CAR-T recombinant expression vector as well as a construction method and an application of the OCTS-CAR-T recombinant expression vector. The PSCA and PD-L1 targeted CAR comprises a CD8 leader membrane receptor signal peptide, a double-antigen binding region, a CD8 Hinge chimeric receptor linker, a CD8 Transmembrane chimeric receptor transmembrane region, a CD28 chimeric receptor co-stimulator, an OX40 chimeric receptor co-stimulator and a TCR chimeric receptor T-cell activation domain which are connected in series sequentially, wherein the double-antigen binding region comprises heavy chains VH and light chains VL of PSCA and PDL1 single-chain antibodies, Inner-Linker in antibodies and Inter-Linker among the single-chain antibodies, which are in series connection or turn connection. Besides, the invention provides the encoding gene of the PSCA and PD-L1 targeted CAR, the recombinant expression vector as well as the construction method and the application of the recombinant expression vector.

The present invention relates to chimeric transmembrane immunoreceptors, named “zetakines,” comprised of an extracellular domain comprising a soluble receptor ligand linked to a support region capable of tethering the extracellular domain to a cell surface, a transmembrane region and an intracellular signalling domain. Zetakines, when expressed on the surface of T lymphocytes, direct T cell activity to those specific cells expressing a receptor for which the soluble receptor ligand is specific. Zetakine chimeric immunoreceptors represent a novel extension of antibody-based immunoreceptors for redirecting the antigen specificity of T cells, with application to treatment of a variety of cancers, particularly via the autocrin / paracrine cytokine systems utilized by human maligancy. In a preferred embodiment is a glioma-specific immunoreceptor comprising the extracellular targeting domain of the IL-13Rα2-specific IL-13 mutant IL-13(E13Y) linked to the Fc region of IgG, the transmembrane domain of human CD4, and the human CD3 zeta chain.

The invention discloses a CD19 specific chimeric antigen receptor. The CD19 specific chimeric antigen receptor is formed by connecting a single-chain antibody of human antibody CD19, CH2CH3 of a human antibody IgG4, a transmembrane domain and intracellular signal structure of CD28, an intracellular signal structure of CD137 and an intracellular signal structure of CD3zeta in series. The invention further discloses an amino acid sequence and a nucleotide sequence of the chimeric antigen receptor. The invention further discloses application of the chimeric antigen receptor in preparation of medicine for treating CD19 related tumors. According to the application, T-lymphocyte is modified, and the modified lymphocyte can be used for treating the CD19 related tumors.

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 relates to a specific chimeric antigen receptor against a human HER 2 antigen, a coding gene, an expression vector and application. The chimeric antigen receptor against the human HER 2antigen comprises a human CD8 leader chimeric receptor signal peptide, a human HER2 single chain antibody, a human CD8 alpha hinge region, a human CD28 intracellular transmembrane region, a human 41BBintracellular region inducible co-stimulator and a human CD3 zeta intracellular signaling structure domain which are sequentially connected. The invention also provides the coding sequence, the recombinant expression vector and a construction method and application of the chimeric antigen receptor against the human HER2. The chimeric antigen receptor can be stably express on T lymphocytes, can specifically recognize and kill HER 2 positive tumor cells, improve the safety of treatment, and can be used for targeted therapy of tumors.

The invention belongs to the field of tumor biological products, and particularly relates to an chimeric antigen receptor, a gene of the chimeric antigen receptor, the recombinant expression vector ofthe chimeric antigen receptor, a CD22-CD19 double-targeting T cell and application of the T cell. The chimeric antigen receptor is CD22ScFv-L-CD19ScFv-CD8-CD137-CD3zeta and comprises CD22ScFv, connecting peptide L, CD19ScFv, a hinge region and a transmembrane region of CD8, an intracellular signal structural domain of CD137 and an intracellular signal structural domain of the CD3zeta which are connected in series. According to the chimeric antigen receptor, the gene of the chimeric antigen receptor, the recombinant expression vector of the chimeric antigen receptor, the CD22-CD19 double-targeting T cell and the application of the T cell, when B-cell line hematological malignant tumors are treated, the T cell modified by the chimeric antigen receptor not only can specifically recognize a tumor cell which is only expressed by a single target spot of a CD19 antigen or a CD22 antigen, but also can recognize tumor cells co-expressed by the two target spots of the CD19 antigen and the CD22antigen, compared with the single target spot CAR T, the double target spots CAR T have stronger anti-tumor activity, so that the immune escape of the tumor cells expressed by the low-abundance antigen is avoided, and therefore the recurrence risk is reduced.

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.