627 results about "Transmembrane domain" patented technology

The invention discloses a CA9-targeted chimeric antigen receptor and application thereof, and belongs to the technical field of biological medicines. The CA9 targeting chimeric antigen receptor provided by the invention comprises a CD8 alpha leading signal peptide, an anti-CA9 single-chain variable fragment, a CD8 alpha hinge, a CD8 transmembrane structural domain and a CD3 zeta intracellular costimulatory signal transduction structural domain. According to the invention, an anti-CA9 single-chain variable fragment is used as an antigen binding structural domain to construct a chimeric antigen receptor (CAR) molecule, the macrophage expressing the anti-CA9CAR can realize specific targeting and phagocytosis killing of CA9 positive kidney cancer cells, and the constructed lipid nanoparticle delivery system can effectively transfer a gene expression vector, so that the gene expression vector can realize effective target site delivery, and the CA9 positive kidney cancer cells can be effectively targeted and killed. The constructed hydrogel-liposome combined drug delivery system has the performance of relieving toxic and side effects, controllable release and hemostasis.

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 belongs to the technical field of biology, and provides a nanometer antibody targeting Nectin-4, and a nucleic acid molecule and an expression vector for coding the nanometer antibody targeting Nectin-4. The invention also provides a chimeric antigen receptor which comprises an extracellular antigen binding domain, a transmembrane domain and an intracellular domain, and the extracellular antigen binding domain is a Nectin-4 nano antibody; the invention also provides a chimeric antigen receptor CAR which contains the nano antibody as scFv and co-expresses CXCR1, a CAR-T cell constructed by the chimeric antigen receptor CAR, and an enhanced CAR-T cell obtained by modifying the CAR-T cell with microbial short-chain fatty acid, so as to improve the infiltration and anti-tumor activity of the CAR-T cell targeting Nectin-4.

Provided herein are isolated polynucleotides encoding a polypeptide comprising an antigen protein fused to a signal sequence and a transmembrane domain, and optionally fused to a ferritin. Also provided herein are isolated polynucleotides encoding alphaviral non-structural proteins nsp1, nsp2, nsp3, and nsp4 and polypeptides comprising an antigen protein fused to a signal sequence and a transmembrane domain, and optionally fused to a ferritin. The antigen may be influenza. Polynucleotides, such as RNAs, can be used as vaccines against influenza infection.

Lipid nanoparticles (LNPs) encapsulating self-amplifying mRNA, compositions, and methods of use of the novel nucleic acid constructs and compositions are disclosed. The LNP constructs comprise a novel ionizable lipid. The novel sa-mRNA constructs encode a modified SARS-CoV-2 spike protein in which the polynucleotide has been truncated to comprise no nucleotides encoding SARS-CoV-2 transmembrane domain and short cytoplasmic domain amino acids, as well as immunomodulators. The sa-mRNA may be used as a therapeutic, diagnostic and / or prophylactic agent for mammalian cells or organs.

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.

The invention discloses preparation and application of a targeting LYPD3 chimeric antigen receptor T cell. The chimeric antigen receptor comprises an LYPD3 antigen binding domain, a transmembrane domain, a costimulatory signal transduction domain and an intracellular signal transduction domain, the LYPD3 antigen binding domain comprises a heavy chain variable region with CDR-H1, CDR-H2 and CDR-H3 and a light chain variable region with CDR-L1, CDR-L2 and CDR-L3, and the CDR-H1, the CDR-H2 and the CDR-H3 are respectively composed of amino acid sequences of SEQ ID NO: 3, SEQ ID NO: 4 and SEQ ID NO: 5. And the CDR-L1, the CDR-L2 and the CDR-L3 are respectively composed of amino acid sequences as shown in SEQ ID NO: 6, SEQ ID NO: 7 and SEQ ID NO: 8.

The present invention relates to a bispecific chimeric antigen receptor targeting CD117 and CD7 and its application, wherein the bispecific chimeric antigen receptor comprises a signal peptide, an antigen binding domain, a hinge region, a transmembrane domain and a signal transduction domain, wherein the antigen binding domain comprises a CD117 binding domain and a CD7 binding domain. The bispecific chimeric antigen receptor provided by the present invention combines targeted antibodies for CD117 and CD7 together, recognizes and binds to two different antigens at the same time, enhances the targeted elimination ability of malignant cells, and by acting on hematopoietic stem cells and immune cells at the same time, can more effectively eliminate tumor cells in the receptor, while retaining or reconstructing normal hematopoietic and immune functions.

The invention relates to the field of biological medicines, in particular to a chimeric cytokine activated receptor for activating lymphocytes by using soluble immunosuppressive molecules and application of the chimeric cytokine activated receptor in tumor treatment. The chimeric cytokine activation receptor and a chimeric antigen receptor for recognizing tumor antigens are connected in parallel to form a co-expressed polycistron structure. Wherein the chimeric cytokine activation receptor comprises an scFv structural domain, a transmembrane structural domain and a cytokine chimeric activation structural domain which specifically recognize and bind soluble immunosuppressive molecules. The CAR-NK cell can specifically recognize soluble inhibitory factors in the tumor microenvironment and improve the in-vivo and in-vitro anti-tumor efficacy of the CAR-NK cell, and can be used for treating solid malignant tumors.

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.

Recombinant proteins that stimulate an immune response in the presence of naturally inhibitory ligand binding are described. The recombinant proteins include an extracellular domain of an inhibitory immune cell protein and an intracellular domain of a stimulatory immune cell protein connected via a transmembrane domain. The recombinant proteins can be used to stimulate immune cell activation in the fight against cancers and infectious diseases, among other uses.

The invention belongs to the technical field of bioengineering, and particularly relates to an IL-12-CD137 chimeric protein, a function-enhanced engineered NK cell, and preparation and application thereof. The IL-12-CD137 chimeric protein comprises a signal peptide, an IL-12a protein molecule, a CD137 transmembrane structural domain and a CD137 intracellular structural domain, and has an amino acid sequence as shown in SEQ ID NO: 1. According to the function-enhanced engineered NK cell, the IL-12-CD137 chimeric protein sequence is introduced into an original NK cell, the function-enhanced engineered NK cell expressing Chime-IL12-CD137 is obtained, the amplification capacity and killing capacity of the NK cell can be enhanced, and the function-enhanced engineered NK cell is applied to treatment of tumor and virus-infected diseases of companion animals for the first time.

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.

The invention discloses a salty and fresh difunctional taste-active peptide as well as a preparation method and application thereof, and relates to the technical field of biology. The amino acid sequence of the salty and fresh difunctional taste-active peptide is as shown in any one of SEQ ID NO.1-4. According to the invention, a compound protease enzymolysis method is adopted to prepare enzymatic hydrolysate rich in salty and fresh dual-function taste-active peptides, a plurality of salty and fresh dual-function taste-active peptides are identified and screened out by utilizing polypeptiomics and a molecular docking technology, and meanwhile, a transmembrane structure domain of a taste receptor is evaluated and predicted; chemical bonds and docking sites for docking of the salty and fresh difunctional taste-active peptide and the taste receptor are analyzed, key chemical bonds and binding sites for interaction of the salty and fresh difunctional taste-active peptide and the salty receptor are summarized, and the salty taste and umami strength of the salty and fresh difunctional taste-active peptide and the salty receptor are evaluated. The salty and fresh dual-function flavor peptide screened by the invention has strong salty taste and fresh taste, can be used as a substitute of sodium salt, and is used for preparing low-salt and low-sodium food. The invention also provides a certain reference for rapidly and simply obtaining the salty and fresh dual-function taste-active peptide.

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 humanized monoclonal anti-human EpCAM antibody, such as a single-chain variable fragment (scFv), comprising VH having the amino acid of SEQ ID NO: 2 and VL having the amino acid of SEQ ID NO: 4. The present invention is also directed to a 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.

The invention relates to an endoplasmic reticulum-based chimeric protein construct for targeting protein degradation and application thereof, for example, the chimeric protein construct is used for treating cancers, virus infectious diseases, autoimmune diseases, neurodegenerative diseases and the like. The chimeric protein constructs comprise an endoplasmic reticulum-related degradation mechanism protein binding domain and a targeting domain. The ERAD mechanism protein binding domain of the chimeric protein construct may be a transmembrane domain of a viral endoplasmic reticulum resident protein or a functional variant thereof and an endoplasmic reticulum resident domain or a functional variant thereof. The targeting domain of the chimeric protein construct can target any target protein of interest, which can be a natural ligand of the target protein, an antibody that specifically recognizes the target protein, or an antigen-binding fragment thereof. The targeting domain of the chimeric protein construct may also be an antigen that can be specifically recognized by an antibody.

The invention relates to an IL5RA cell surface marker. A cell tag comprising an extracellular region, a transmembrane region, and optionally an intracellular region is provided. The extracellular region comprises an IL5 receptor alpha (IL5Ra) sequence linked to a transmembrane domain, and the recombinant polypeptide cannot function in signal transduction. The cell tag can be operably linked to a transgene. Expression of the cell tag allows for the identification, detection, selection, and ablation of cells expressing the transgene and the cell tag. In some embodiments, the genetically modified host cell comprises a transgene comprising a polynucleotide encoding a chimeric antigen receptor comprising a ligand binding domain and a polynucleotide encoding a cell tag. Pharmaceutical formulations produced by the methods and methods of using the pharmaceutical formulations are also described.

The present invention provides compositions and methods for treating cancer in a human. The invention includes relates to administering a genetically modified T cell expressing a CAR having an antigen binding domain, a transmembrane domain, a CD2 signaling domain, and a CD3 zeta signaling domain. The invention also includes incorporating CD2 into the CAR to alter the cytokine production of CAR-T cells in both negative and positive directions.

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.

The present disclosure provides an anti-IL13RA2 single domain antibody (e.g., a VHH domain antibody), and a chimeric antigen receptor (CAR) that binds IL13RA2, the chimeric antigen receptor comprising: the anti-IL13RA2 single domain antibody 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 in cancer immunotherapy.

The invention belongs to the technical field of biology, and relates to an RSV pre-F mutant as well as a preparation method and application thereof. Relative to a wild type F0 polypeptide, the RSV pre-F mutant meets the following conditions: (1) the RSV pre-F mutant does not contain a furin enzyme cutting site fragment, a P27 polypeptide, a transmembrane structural domain and an intracellular structural domain; (2) the gene has mutations of S180C, S186C, A170C, V179C, A241C, Q279C, D486C and A490C; and (3) the C end of the F1 polypeptide is not connected or is connected with an aggregation motif. The conformations of the mutant and the trimer thereof are highly stable, the mutant and the trimer thereof can be self-assembled to form the trimer without depending on a heterotrimer structural domain, a high-level binding antibody and a neutralizing antibody can be induced after immunization, and the situation that the high-level binding antibody with non-neutralizing activity is generated when the heterotrimer structural domain is immunized is avoided, so that the quality of the antibody is improved.

Provided is a fusion protein, comprising IL-10 and a transmembrane domain, wherein the fusion protein is expressed on an immune cell, and the immune cell does not comprise a regulatory T cell. Also provided is a modified immune cell, comprising a fusion protein and an antigen recognition receptor, wherein the fusion protein comprises IL-10 and a transmembrane domain, and the immune cell does not comprise a regulatory T cell. Also provided is a use of the fusion protein and the modified immune cell in prevention and / or treatment of diseases.

The invention relates to an application of a macrophage expressing an anti-uPAR chimeric antigen receptor in preparation of an anti-aging drug, and discloses a new application of the macrophage (CAR-M) expressing the anti-uPAR chimeric antigen receptor in senescence diseases, and the mechanism is that uPAR positive cells are specifically recognized and apoptosis of the uPAR positive cells is induced by targeting senescence cell surface antigen uPAR. According to the uPAR-CAR-M, a humanized anti-uPAR single-chain antibody is used as a chimeric antigen receptor recognition region, so that the chimeric antigen receptor has high specificity, and the chimeric antigen receptor is used for promoting the functions of macrophages by using a CD8 alpha transmembrane structural domain, a CD28 costimulatory molecule and a Megf10 sequence, so that a better killing effect is given to the CAR-M. The problems of inflammatory microenvironment caused by abnormal aggregation of senescence cells, chronic tissue damage and senescence-related disease treatment disorder are solved, and the application value for treating senescence-related diseases (such as osteoarthritis and the like) expressing uPAR is important.

The present invention includes compositions and methods for retrieving tumor-related antibodies and antigens. In one aspect, the invention includes a method for Sequential Tumor-related Antibody and antigen Retrieving (STAR) which directly and efficiently identifies potent antibodies that can specifically bind to tumor-related antigens on the tumor cell surface. In another aspect, the invention includes a CAR comprising a nanobody, a transmembrane domain, and an intracellular domain, wherein the nanobody is retrieved by a STAR method. In another aspect, the invention includes a CAR T system that targets CD13 and treats acute myeloid leukemia. In another aspect, the invention includes a CAR T system and ADC that targets CDH17 and treats NETs and other types of tumors expressing this antigen, with tolerable toxicities.

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 invention discloses a chimeric antigen receptor targeting an HIV infected cell, a CAR-T cell and application. The chimeric antigen receptor comprises an antigen binding domain, a chimeric receptor hinge region, a transmembrane domain, a costimulatory signal transduction domain and a signal transduction domain, the antigen binding structural domain is an anti-HIV monoclonal antibody JSR771 and is composed of a heavy chain VH and a light chain VL, the amino acid sequence of the heavy chain VH is as shown in SEQ ID NO.1, and the amino acid sequence of the light chain VL is as shown in SEQ ID NO.2. The invention further discloses a preparation method of the anti-HIV monoclonal antibody JSR771. By optimizing the separation, activation, transduction and culture conditions of the T cells and strictly controlling the quality control standard, the prepared anti-HIV-1CAR-T cells have high motility, high specificity and strong killing ability, and a new hope is provided for clinical treatment of HIV infection.

An embodiment of the invention provides a chimeric antigen receptor (CAR) comprising an antigen binding domain specific for FLT3, a transmembrane domain, and an intracellular T cell signaling domain. Nucleic acids, recombinant expression vectors, host cells, populations of cells, antibodies, or antigen binding portions thereof, and pharmaceutical compositions relating to the CARs are disclosed. Methods of detecting the presence of a proliferative disorder, e.g., cancer, in a mammal and methods of treating or preventing a proliferative disorder, e.g., cancer, in a mammal are also disclosed.

A series of recombinant DNA constructs and a method is disclosed for use in immunological therapy in general; and in disrupting T cell receptor (TCR), human leukocyte antigens (HLA) class I and NKG2D (Natural-Killer Group 2, member D) ligand expression in particular, with the effect of producing highly compatible autologous universal T cells for further genetically engineering for allogeneic administration. A Universal T (UT) construct is provided and used, comprising a TCR antibody fragment fused to a transmembrane domain (TMD) and ER retention domain of adenovirus early region 3 glycoprotein E3-19k (E3 / 19K) (TCR-E3 / 19K RD). The Universal T (UT) construct can hijack ERAD machinery to arrest TCR and HLA molecules in endoplasmic reticulum (ER) and facilitate their translocation into the cytoplasm for ubiquitination and degradation by proteasomes.