336 results about "Transmembrane domain" patented technology

The present disclosure provides bispecific chimeric antigen receptors that target BCMA and CD19. The CAR may comprise an scFv targeting BCMA and an scFv targeting CD19, a hinge region, a transmembrane domain, a co-stimulatory region, and a cytoplasm signaling domain. Chimeric antigen receptors can be used to treat autoimmune disorders or cancer.

A chimeric autoantibody receptor (CAAR) that enables targeting of an immune cell to autoantibody producing B cells. The CAAR includes an autoantigen or fragment thereof that is bound by autoantibodies associated with neurological autoimmune disease primarily targeting the central nervous system. Also disclosed is a nucleic acid molecule encoding a chimeric autoantibody receptor (CAAR), the nucleic acid sequence encoding an autoantigen or fragment thereof that is bound by autoantibodies associated with a neurological autoimmune disease primarily targeting the central nervous system, a transmembrane domain, and an intracellular signaling domain, a vector comprising a nucleic acid molecule encoding a chimeric autoantibody receptor (CAAR), a genetically modified immune cell comprising the nucleic acid molecule encoding the CAAR and use of the immune cell in the treatment or prevention of a neurological autoimmune disease primarily targeting the central nervous system, such as an autoimmune encephalopathy or encephalomyelopathy, preferably anti-NMDAR encephalitis.

Provided herein is a recombinant protein comprising a transmembrane domain derived from a transmembrane domain of a wild type erythropoietin receptor (EPOR). Nucleic acid molecules encoding such recombinant proteins, recombinant constructs, vectors and cells containing the nucleic acid molecules, methods of producing such cells and therapeutic uses thereof are also provided.

Provided herein are cell surface receptors that include an extracellular binding domain, a transmembrane domain, an intracellular signaling domain, and a protease cleavage site disposed between the extracellular binding domain and the intracellular signaling domain. In certain aspects, the cell surface receptors are engineered cell surface receptors, such as chimeric antigen receptors (CARs). Also provided are cells that include such receptors (e.g., where the cells express the receptors on their surface) and pharmaceutical compositions including such cells. Nucleic acids that encode the cell surface receptors, cells including such nucleic acids, and pharmaceutical compositions including such cells, are also provided. Also provided are methods for regulating signaling of a cell surface receptor, and methods of using the cells of the present disclosure, including methods of using such cells to administer a regulatable cell-based therapy to an individual.

The present disclosure provides compositions and methods for altering auxin accumulation in corn or maize plants. Methods and compositions are also provided for altering the expression of genes related to auxin efflux through editing or mutagenesis of a brachytic2 (br2) gene to introduce a premature stop codon or a deletion into the gene such that a truncated Br2 protein encoded by the mutant allele of the br2 gene, which may be a dominant or semi-dominant allele, has at least part of a transmembrane domain without a nucleotide binding domain or motif. Modified plant, plant parts and cells having such a mutant allele with reduced or altered expression or activity of a br2 gene product can have improved characteristics, such as reduced plant height and increased lodging resistance, but without off-types in the plant.

Described herein are engineered cytokine receptor switches that can include a signal peptide, an extracellular activator binding domain, a hinge, a transmembrane domain, and / or an intracellular signaling domain. Binding of an activator to the activator binding domain can activate cytokine signaling through the intracellular signaling domain. These cytokine receptor switches can be expressed in immune cells, sometimes in combination with a chimeric antigen receptor (CAR), to increase immune cell persistence by promoting adoption of memory-like phenotypes. Also described herein are methods of using engineered cytokine receptors in immune cell therapies, such as CAR T-cell therapy, to improve patient outcomes and prevent disease relapse.

The present invention is directed to a monoclonal anti-human CS1 clone 7A8D5 antibody or a single-chain variable fragment (scFv), comprising VH having the amino acid of SEQ ID NO: 4 and VL having the amino acid of SEQ ID NO: 5. The present invention is also directed to a chimeric antigen receptor fusion protein comprising from N-terminus to C-terminus: (i) CS1 scFv of the present invention, (ii) a transmembrane domain, (iii) at least one co-stimulatory domains, and (iv) an activating domain.

A membrane assembly comprising: (a) a porous support; and (b) a plurality of membrane mimetic structures on a surface of the support; wherein the membrane mimetic structures comprise: (i) a channel protein which comprises a transmembrane domain having a hydrophobic surface, and (ii) one or more amphiphilic molecules; and wherein the one or more amphiphilic molecules form a ring structure around the hydrophobic surface of said transmembrane domain of the channel protein.

The invention relates to a chimeric T-cell receptor (TCR) comprising a human transmembrane domain, a human intracellular domain and a human intracellular CD3ε domain wherein in at least one of the CD3ε domains, an arginine (R) amino acid residue at position 53 and / or 54 of SEQ ID NO:25, or an arginine (R) amino acid residue at a position that corresponds to said arginine (R) amino acid residue at position 54 of SEQ ID NO:25, is substituted or deleted. The invention further relates to a method of producing a T-cell expressing the chimeric co-stimulatory TCR. The invention further relates to a chimeric T-cell receptor (TCR) comprising a human co-stimulatory domain and a human CD3ε domain. The invention further relates to a method of treating a patient having a tumor or an immune-related disease comprising administering T-cells expressing the chimeric TCR to the patient.

The present invention inter alia relates to a chimeric transmembrane receptor comprising a polypeptide, wherein the polypeptide comprises at least one T cell immunoreceptor with Ig and ITIM domains (TIGIT) polypeptide region comprising a TIGIT extracellular ligand binding domain; further wherein the polypeptide comprises at least one non-TIGIT polypeptide region, wherein the at least one non-TIGIT polypeptide region comprises a transmembrane polypeptide region of CD2, CD40, HVEM, or CD30, and wherein the at least one non-TIGIT polypeptide region comprises at least one costimulatory cytoplasmic polypeptide domain, region or motif of CD2, CD40, HVEM, or CD30, or wherein the transmembrane domain is from TIGIT and further wherein the at least one non-TIGIT polypeptide region comprises at least one costimulatory cytoplasmic polypeptide domain, region or motif of CD2 or CD28. The invention also relates to corresponding nucleic acids, vectors and T-cells comprising or expressing the chimeric receptors, to a pharmaceutical composition comprising the T-cells, and to methods for preparing a T-cell for immunotherapy and for treating a disease, respectively, wherein the chimeric transmembrane receptor is used.

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.

The invention discloses a genetically engineered bacterium and an application of the genetically engineered bacterium in production of farnesene. The genetically engineered bacterium takes saccharomyces cerevisiae as a chassis strain; an exogenous beta-farnesene synthase gene is integrated, an ERG9 gene is knocked out, a promoter of a truncated HMG1 gene is replaced with an ANB1 promoter, an exogenous transhydrogenase gene is integrated and driven by a glucose sensitive promoter, beta-farnesene synthase is mutated and fused with a transmembrane structural domain of ABC transporter protein PDR10, and then a chimeric expression unit is constructed. According to the present invention, the chassis bacteria are modified by at least one of the steps of overexpression of phosphatidylcholine synthetase, knockout of sterol ester synthetase and introduction of exogenous alkyl glycerol monooxygenase, and the obtained engineering bacteria are combined with the optimized fermentation process so as to significantly improve the farnesene synthesis efficiency and the production economy; therefore, the genetically engineered bacterium and the fermentation method provided by the invention have good application prospects.

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.

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 provides ROR1 specific chimeric antigen receptors (CAR) and their therapeutic use. The CAR comprises a signal peptide, a ROR1 antigen binding domain, a hinge, a transmembrane domain, a co-stimulatory domain and an intracellular signaling domain. The modified immune cells endowed with such CARs are suitable for treating malignancies such as cancer, chronic lymphocyte leukemia (CLL), and acute lymphocytic leukemia (ALL).

The present invention is directed to a humanized BCMA single-chain variable fragment (scFv), comprising VH having the amino acid sequence of SEQ ID NO: 4 and VL having the amino acid sequence of SEQ ID NO: 5. The present invention is also directed to a BCMA chimeric antigen receptor fusion protein comprising from N-terminus to C-terminus: (i) a single-chain variable fragment (scFv) of the present invention, (ii) a transmembrane domain, (iii) at least one co-stimulatory domains, and (iv) an activating domain. This humanized BCMA-CAR-T cells have specific killing activity with secretion of cytokine IFN-gamma in CAR-T cells in vitro and in vivo.

Chimeric antigen receptors (CARs) and bicistronic chimeric antigen receptors (BiCisCARs) that target fibroblast growth factor receptor 4 (FGFR4), CD276, or both are disclosed. The CARs and BiCisCARs include a hinge and transmembrane domain from either CD28 or CD8 and a co-stimulatory domain from either CD28 or 4-1BB. The CARs and BiCisCARs can further include amino acid substitutions in one or more immunoreceptor tyrosine-based activation motifs (ITAMs) of a CD3ζ intracellular signaling domain. Cells expressing the CARs or BiCisCARs can be used for the treatment of cancers that express one or both of FGFR4 and CD276.

The invention relates to a CD19 and CD70 targeted double-target chimeric antigen receptor and application thereof, the CD19 and CD70 targeted double-target chimeric antigen receptor comprises an extracellular antigen binding domain, a hinge region, a transmembrane domain, an intracellular costimulatory domain and an intracellular signal transduction domain, and the extracellular antigen binding domain has specific binding ability to CD19 and CD70. The double-target chimeric antigen receptor structure has a treatment effect of targeting double antigens or single antigens, can be used for preparing immune effector cells targeting CD19 and CD70, and provides a treatment or improvement approach for diseases related to CD19 and CD70 double expression or CD19 / CD70 single expression.

An engineered trophoblast that expresses a cell surface molecule that specifically recognizes NKp46, the cell surface molecule comprising at least an antibody targeting NKp46 and a transmembrane domain. The invention discloses a cell culture medium and a method for amplifying NK cells. Compared with unengineered trophoblasts, the engineered trophoblasts are used for activating NK cells, and the amplification capacity of the NK cells and the killing activity of tumor cells can be enhanced.

The present disclosure provides a polynucleotide comprising an expression cassette of a membrane protein linked to one or more additional expression cassettes for expressing one or more additional genes, the expression cassette of the membrane protein comprising a transmembrane domain and an extracellular domain, the extracellular domain comprising a recognition sequence, and one or more additional expression cassettes for expressing one or more additional genes, the one or more additional expression cassettes being linked to the one or more additional expression cassettes. The recognition sequence can be specifically recognized by the antibody of the recognition sequence. The invention also provides a vector and a cell containing the polynucleotide, and a method for transferring an exogenous gene into a cell and screening the cell by using the polynucleotide or the vector.

The invention belongs to the field of biological medicine, and discloses a membrane binding type IL7 fusion protein, an engineered immune cell for expressing the membrane binding type IL7 fusion protein and application of the membrane binding type IL7 fusion protein. The fusion protein comprises an IL7 region and a transmembrane domain and can be expressed on a cell membrane, the tumor cell killing ability and the T cell survival ability of T cells expressing the fusion protein are both enhanced, and the aims of improving the tumor immune cell treatment effect and reducing the toxic and side effects are achieved. Particularly, the IL7 fusion protein anchors and expresses IL7 on the surface of a cell through transmembrane domains such as CD80 or PD-L1 and the like, so that (1) immune cells can be accurately regulated and controlled, the possibility that an excessive IL7 signal possibly causes autoimmune response or aggravates CRS is reduced, and the safety of the IL7 to immune cells such as T cells and the like is enhanced; (2) the half-life period of IL7 is prolonged, and the anti-tumor effect of adoptive immune cells is enhanced; and (3) the transmembrane fragment is linked with the IL7 through a hinge region of the flexible linker G4S, CD80 or PD-L1, so that the flexibility of the IL7 is enhanced, and the proliferation and killing functions of the IL7 on T cells are enhanced.

Provided herein are novel synthetic pathway activators comprising multimerization regions, transmembrane domains, and intracellular signaling domains.

The invention provides a chimeric antigen receptor for regulating and controlling a signal time sequence and application of the chimeric antigen receptor. The chimeric antigen receptor sequentially comprises a signal peptide, an extracellular domain, a transmembrane domain and an intracellular domain from an N terminal to a C terminal, the extracellular structural domain comprises an antigen recognition region and a hinge region; the intracellular domain comprises a costimulatory signal transduction region and a CD3 [zeta] intracellular region variant; the CD3 [zeta] intracellular region variant comprises three ITAMs, and the arrangement sequence of the ITAMs is ITAM3-ITAM2-ITAM1 from the N end to the C end. Compared with a conventional chimeric antigen receptor containing a wild CD3 zeta intracellular region, the chimeric antigen receptor provided by the invention can significantly enhance the functional activity of immune cells expressing the chimeric antigen receptor, which is specifically embodied in stronger multiplication capacity and durability, and significantly improves the antigen sensitivity and targeted killing efficacy.

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 invention relates to a novel human immunodeficiency virus envelope protein antigen expressed by mammals. Various embodiments of the invention relate to a polypeptide comprising 1-10 epitopes or more of the HIV envelope protein and a fusion protein, wherein the polypeptide lacks a transmembrane domain of the HIV gp41 protein. Such polypeptides can be expressed in mammalian cells, such as human cells, to produce polypeptides useful, for example, in the development of novel anti-HIV antibodies. The polypeptides described herein and the novel antibodies developed therefrom are generally useful in medical diagnostics, and they can also be used in the prophylactic and therapeutic treatment of HIV.

Disclosed is a nucleic acid encoding a chimeric antigen receptor comprising an extracellular domain including an antigen recognition domain consisting of a fully human single variable heavy chain (VH) domain that binds to a first epitope on B-cell maturation antigen (BCMA), a transmembrane domain, and an intracellular domain including a signaling domain.

The present application relates to a multispecific single-domain antibody chimeric antigen receptor and T cell engager, nucleic acid, expression cell thereof, use thereof, and pharmaceutical composition for treating cancer. The multispecific single-domain antibody chimeric antigen receptor and T cell engager comprises an HLA-G single-domain antibody chimeric antigen receptor and a bispecific T cell engager, wherein the HLA-G single-domain antibody chimeric antigen receptor comprises an HLA-G single-domain antibody unit, a transmembrane domain, and a CD3z signaling domain, and the bispecific T cell engager comprises a PD-L1 single-domain antibody unit and a CD3e single-domain antibody. The multispecific single-domain antibody chimeric antigen receptor and T cell engager can induce tumor cell death and has an excellent effect of inhibiting tumor growth, thereby being useful for preparing a medicament for inducing tumor cell death in a mammal and as a pharmaceutical composition for treating cancer.

A hybrid protein comprises a first domain comprising a sequence encoding a surface protein of an enveloped RNA virus and a second domain comprising a sequence encoding an ectodomain of a type 2 transmembrane domain protein, wherein the second domain is located at the C-terminal of the first domain. The hybrid protein or an mRNA encoding such protein can be used as a vaccine against the infection of the enveloped RNA virus.