242 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.

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 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.

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 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.

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.

The present invention provides chimeric antigen receptors (CARs) comprising an extracellular domain which specifically binds to Mesenchymal Epithelial Transition factor (MET); a transmembrane (TM) domain; a co-stimulatory signaling domain; and, a primary intracellular signaling domain. The application further relates to polynucleotides and recombinant vectors encoding the CARs, as well as to host cells and methods for producing host cells that express the CARs. The application further relates to pharmaceutical compositions comprising the CAR modified cells. Methods for stimulating elimination of a MET-expressing cell and for treating a MET-positive cancer using the CAR modified cells in a subject are also disclosed.

This disclosure provides a recombinant hepatitis C virus glycoprotein comprising heterodimers of E1 and E2 glycoproteins having at least 60% homology with SEQ ID No. 1, engineered furin protease cleavage sites, and hydrophilic amino acid linkers, wherein the E1 and E2 glycoproteins partially or completely lack their respective transmembrane domains. This document further provides nucleic acids encoding the recombinant hepatitis C virus glycoprotein, nanoparticle conjugates comprising the recombinant hepatitis C virus glycoprotein, and compositions comprising the recombinant hepatitis C virus glycoprotein, the nucleic acid, or the nanoparticle conjugate. Applications of the recombinant hepatitis C virus glycoprotein or compositions comprising the glycoprotein are also envisioned.

The invention relates to a chimeric autoantibody receptor (CAAR) comprising an autoantigen of a Contactin-associated protein-like 2 (CASPR2) protein or one or more autoantigenic fragments thereof. The invention relates further to a nucleic acid molecule encoding a chimeric autoantibody receptor (CAAR), the nucleic acid comprising a sequence encoding an autoantigen, wherein said autoantigen comprises or consists of Contactin-associated protein-like 2 (CASPR2) or one or more fragments thereof, a sequence encoding a transmembrane domain, and a sequence encoding an intracellular signaling domain. The invention further relates to a nucleic acid vector comprising a nucleic acid molecule encoding the chimeric autoantibody receptor (CAAR) of the invention. The invention relates further to a genetically modified cell comprising a nucleic acid molecule or a vector of the invention and / or expressing a CAAR according to the invention.

The invention discloses a chimeric antigen receptor targeting EGFRvIII and application of the chimeric antigen receptor. The chimeric antigen receptor sequentially comprises an EGFRvIII targeting nucleic acid aptamer, a transmembrane domain and an intracellular signal domain from an N end to a C end, the EGFRvIII targeted nucleic acid aptamer is an EGFRvIII specific DNA aptamer obtained on the basis of SELEX (systematic evolution of ligands by exponential enrichment) screening, can only be combined with an extracellular domain of the EGFRvIII, and is not combined with an EGFR (epidermal growth factor receptor) wild type; the intracellular signal domain comprises a costimulatory signal domain and an activation signal domain, the C end of the costimulatory signal domain is connected with the N end of the activation signal domain, and the EGFRvIII specific nucleic acid aptamer screened based on SELEX is adopted as a targeting domain, can only be specifically combined with the extracellular domain of EGFRvIII positive tumor cells, and is not subjected to cross combination with EGFR wild cells and normal cells, so that the EGFRvIII specific nucleic acid aptamer can be used for detecting EGFRvIII positive tumor cells, and the EGFRvIII specific nucleic acid aptamer can be used for detecting EGFRvIII positive tumor cells. The problem of off-target killing caused by the fact that a common antibody scFv fragment of a traditional chimeric antigen receptor (CAR) is easily combined with a wild type EGFR is fundamentally avoided.

The present invention provides methods and compositions based on a non-naturally occurring nucleic acid construct encoding a fusion protein for quantifying secretion levels in an individual cell, which may comprise a protein sequence comprising a cytoplasmic domain, a transmembrane domain, and a vesicular domain, wherein the vesicular domain may comprise a sequence of protein marks, wherein upon expression of the fusion protein by a cell, the fusion protein localizes to the membrane of a secretory vesicle such that the protein mark is located in the lumen of the secretory vesicle, and wherein the protein mark binds to a cell-impermeable marker;whereby, after the secretion of the contents of the secretory vesicle, the protein tag is exposed to the cell-impermeable marker, the fusion protein is recycled back into the cell, and the individual cell is tagged with the marker in relation to the amount of secretion.

In the present invention, there is discovered a novel mRNA vaccine for preventing respiratory syncytial virus (RSV) infections, the mRNA vaccine being superior in terms of immunogenicity and pharmacological efficacy compared with RSV FG chimeric protein vaccines each comprising RSV F and G proteins and mRNA vaccines which have been produced on the basis of Japanese Patent No. 7253034 (Patent Document 7). In the present invention, an RSV FG chimeric mRNA vaccine is produced by inserting a highly conserved domain of the RSV G protein into a basic skeleton that is formed by linking a transmembrane region to an RSV F protein ectodomain. As a result of performing evaluation on immunogenicity and pharmacological efficacy, it has been confirmed that the immunogenicity and pharmacological efficacy of the RSV FG chimeric mRNA vaccine of the present invention are superior compared with those of the RSV FG chimeric protein vaccines and mRNA vaccines which have been produced on the basis of Patent Document 7.

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. A preferred co-stimulatory domain is CD28 or 41-BB. The humanized BCMA-CAR-T cells have specific killing activity with secretion of cytokine IFN-gamma in CAR-T cells in vitro and in vivo.

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.

This invention discloses a method for designing transmembrane regulatory proteins based on cueing strategies and generative models, belonging to the field of bioinformatics. It includes a target survey stage and a closed-loop design stage. In the target survey stage, a generative diffusion model is used to generate virtual probes targeting the membrane protein. A set of complex conformations is obtained by combining sequence design and structure prediction models, and binding hotspot regions are identified based on the spatial distribution density of the probes, overcoming the dependence on manually specified binding sites. In the closed-loop design stage, based on the identified hotspot regions, an initial backbone is generated using a generative diffusion model. A structure cueing strategy guides the sequence design and structure prediction models to perform closed-loop iterative optimization, generating sequences that selectively bind to the transmembrane domains of membrane proteins and regulate their functions. This invention achieves automated, function-guided design of transmembrane regulatory proteins, effectively expanding the range of designable targets and significantly improving the stability and functional specificity of the designed products in the membrane environment.

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.