177 results about "Ectodomain" patented technology

The present invention relates, in general, to polypeptides capable of binding and neutralizing transforming growth factor beta (TGF-beta) ligands, and uses of these polypeptides for treating disorders related to TGF-beta expression or activation (e.g. cancer and fibrotic diseases), and methods of making such molecules.

The present invention relates to 4-1BB ligand (4-BBL) extracellular domain (ECD) muteins having reduce affinity for its cognate receptor 4-1BB. The 4-1BBL ECD muteins can be present in homo- or heterotrimeric fusion protein comprising three 4-1BBL ECD monomers. The invention further relates conjugates of such the 4-BBL ECD muteins with a heterologous moiety, such as an antigen binding protein. The antigen-binding regions comprised in the antigen binding protein in the conjugates preferably are specific for a tumor-associated antigen (TAA). In addition to a 4-BBL ECD mutein, the conjugates can comprise further NK cell-activating cytokines, such an IL-21 receptor agonist. The conjugates can further comprise an antigen-binding region that has affinity for a surface antigen expressed on NK cells, e.g. CD16A. Alternatively, the conjugates can further comprise an antigen-binding region that specifically binds an epitope of a γδ TCR. The conjugates of the invention specifically redirect and activate NK cells or γδ T cells to lyse targeted tumor cells. The invention further relates to the use of the 4-BBL ECD muteins and conjugates thereof in the treatment of cancer, preferably a cancer expressing the TAA.

The invention relates to a mutant PD1 extracellular domain fragment and CAR and NK cells containing the fragment. Specifically, the invention provides a polypeptide which is the mutant PD1 extracellular domain fragment and contains an amino acid sequence as shown in SEQ ID NO: 1 or consists of the amino acid sequence as shown in SEQ ID NO: 1. The CAR provided by the invention contains the polypeptide. The invention also provides an NK cell for expressing the CAR. The tumor cell killing capacity of the NK cell expressing the CAR containing the mutant PD1 extracellular domain is obviously higher than that of the NK cell expressing the CAR containing the wild type PD1 extracellular domain.

This invention provides a human antibody with neutralizing ability against the JN.1 variant of SARS-CoV-2 and its application, belonging to the field of biomedical technology. The antibody comprises a heavy chain sequence as shown in SEQ ID NO:1 and a light chain sequence as shown in SEQ ID NO:2; or comprises a heavy chain sequence as shown in SEQ ID NO:3 and a light chain sequence as shown in SEQ ID NO:4. The antibody of this invention binds to the extracellular domain of the JN.1 variant spike protein via ECG. 50 The value was significantly lower than that of its parent antibody, with a binding capacity increase of 3 to 5 times or more. In the pseudovirus neutralization experiment, the antibody showed a half-maximal neutralizing concentration (IC50) against JN.1 pseudovirus. 50 The antibody also showed significantly better performance than the parent antibody, with a neutralizing activity increase of 3 to 24 times or more. Furthermore, the antibody's melting temperature exceeded 75°C, demonstrating good thermal stability.

Described herein are immunoassay methods ("PRO-C17 assay") for measuring the extracellular domain levels of XVII collagen present in a patient sample, which can be used to detect and / or monitor cancer and / or assess the severity of cancer in a patient. Monoclonal antibodies and assay kits suitable for carrying out the methods are also described.

Herpesviridae glycoprotein B (gB) polypeptides comprising a modified ectodomain is stabilized in the prefusion state, enabling development of inhibitors and vaccines directed against these viral pathogens. Modifications to DI, DII, and DV subdomains are important to stabilization of gB in the prefusion state, and additional modifications result in a further improved stabilization of gB in the prefusion state. The gB can be derived from an Epstein Barr Virus (EBV), a Human Cytomegalovirus (CMV), a Human Herpesvirus 6 (HHV6), a Herpes Simplex Virus 1 (HSV1), or a Varicella Zoster Virus (VZV). Polypeptides, nucleic acid constructs, compositions, and methods of using same to elicit an immune response are described.

The invention relates to the technical field of vaccines, and particularly discloses a recombinant extracellular domain mutant trimer of a respiratory syncytial virus pre-fusion F protein, application of the recombinant extracellular domain mutant trimer and a vaccine. The mutant trimer comprises three recombinant F2-F1 extracellular domain protomers, and the recombinant F2-F1 extracellular domain protomers comprise three recombinant F2-F1 extracellular domain In some embodiments, the recombinant F2-F1 extracellular domain protomers each comprise a deletion of positions 104-144 and a peptide linker between positions 103 and 145, and comprise a L373R substitution and an engineered disulfide bond consisting of 55C and 188C, 149C and 458C substitutions, relative to a reference sequence. The recombinant extracellular domain mutant trimer of the F protein before fusion of the respiratory syncytial virus, provided by the invention, has higher yield, and the immunogenicity and stability of the antigen are further improved.

The present disclosure relates to biologically active molecules comprising a single domain antibody (sdAb) that specifically binds to the extracellular domain of human gp130, compositions comprising such antibodies, and methods of use thereof.

This invention discloses an engineered CAR-T cell targeting HIF-1α and its application in tumor immunotherapy. The CAR-T cell expresses a chimeric antigen receptor regulated by the hypoxia-responsive element HRE promoter, with its extracellular domain specifically binding to HIF-1α and its intracellular domain employing the 4-1BB+CD3ζ signaling module. Simultaneously, through immune checkpoint knockout and cytokine / chemokine modification, it achieves hypoxia-dependent activation, anti-exhaustion, high infiltration, and strong killing effects. The CAR-T cells of this invention significantly improve the adaptability to the solid tumor microenvironment and therapeutic efficacy, reduce off-target toxicity, and can be used to prepare drugs for treating malignant tumors such as lung cancer, liver cancer, pancreatic cancer, colorectal cancer, and glioblastoma, possessing significant clinical translational value.

The invention belongs to the technical field of tumor immunotherapy, and relates to an anti-Claudin18.2 single-domain antibody, a multifunctional fusion protein, a recombinant natural killer cell (CT-CAR-NK), and preparation and application thereof. Through alpaca immunization and phage display library construction and panning, the single-domain antibody VHH-C18.2-1 specifically combined with Claudin18.2 is obtained, and the amino acid sequence of the single-domain antibody VHH-C18.2-1 is SEQ ID NO: 1. The amino acid sequence of the designed fusion protein is SEQ ID NO: 3, the fusion protein sequentially comprises a VHH-C18.2-1, a flexible Linker, a TGF-beta RII extracellular domain, a CD8alpha hinge region, a CD8alpha transmembrane region, a 4-1BB intracellular domain and a CD3zeta intracellular domain from the N end to the C end, and the fusion protein has the functions of targeting, resisting TGF-beta inhibition and activating signals. The fusion protein gene transfects human peripheral blood CD56 + CD3-NK cells through lentivirus to obtain CT-CAR-NK, in-vitro verification shows that the CT-CAR-NK still keeps efficient killing in an immunosuppression environment, tumor growth can be remarkably inhibited in vivo, the lifetime can be prolonged, and a safe and efficient scheme is provided for Claudin18.2 positive solid tumor treatment.

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 relates to synthetic designs or chimeric proteins for pseudotyping baculovirus (Autographa californica nuclear polyhedrosis virus) with the rabies virus glycoprotein G (gG) on its surface (Bac::gG-FL), which can be used in anti-rabies vaccine formulations. The chimeric protein is designed from a gene cassette containing gene fragments of the ectodomain of the G glycoprotein of the Pasteur strain rabies virus, a linker of 7 amino acids (GGGGSGG), as well as transmembrane (TM) and cytoplasmic (CT) regions of the gp64 baculovirus protein, with the arrangement of the sequences in the designed gene cassette being shown in figure 1.

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.

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.

Chimeric antigen receptor (CAR) linking molecules and protein entities and dimers comprising an extracellular domain of an antigen present on a cancer cell and a first immune cell effector domain are disclosed, as well as their use in co-treatment of cancer with CAR immune cells.

The application discloses a kind of chimeric proteins, including cytokine and cytokine receptor extracellular domain;Cytokine is embedded in the chimeric region of cytokine receptor extracellular domain, and the chimeric region is located in the flexible connection region of cytokine receptor extracellular domain, or the chimeric region is located in the flexible connection region of the cytokine of cytokine receptor extracellular domain embedded in this cytokine.The application discloses that by selecting suitable chimeric region on CD25 and IL-2 protein, two proteins are divided into different peptide segments, are connected to form a peptide chain, and are expressed to form chimeric protein.It has eliminated or reduced affinity for high-affinity IL-2 receptor (IL-2Rαβγ), and retains / enhances the affinity for medium-affinity IL-2 receptor (IL-2Rβγ).The application also discloses chimeric proteins of IL15RA and IL-15 and chimeric proteins of IL21R and IL21.The application also discloses conjugates, pharmaceutical compositions, nucleic acid molecules, expression vectors, host cells, production methods, kits of the chimeric protein, and uses thereof.

There remains a need for effective therapeutic agents for the treatment of TGFβ superfamily-associated disorders. [Solution] Polypeptides comprising an activin receptor type IIB (ActRIIB) ectodomain (ECD) variant are provided. In some embodiments, the polypeptides of the present disclosure comprise an ActRIIB-ECD variant fused to an Fc domain portion. The present disclosure also provides pharmaceutical compositions and methods using the polypeptides to treat diseases and conditions associated with TGF-β superfamily ligand signaling, such as metabolic disorders, diabetes, obesity, cardiometabolic disease, pulmonary hypertension, fibrosis, muscle weakness and atrophy, bone damage, and / or low red blood cell levels (e.g., anemia).

The present invention relates to a mutant polypeptide comprising the amino acid sequence of the ectodomain of glycoprotein G of a vesicular stomatitis virus (VSV) strain, wherein said ectodomain comprises the amino acid sequence as set forth in SEQ ID NO: 2 or a sequence having at least 50% of identity with the amino acid sequence as set forth in SEQ ID NO: 2, with at least one substitution of an amino acid residue selected from the group consisting of: a) any amino acid residue located from position 421 to position 429 and any amino acid residue located from position 17 to position 25 of SEQ ID NO:2; or b) any amino acid residue located from a position equivalent to position 421 to a position equivalent to position 429 of SEQ ID NO: 2 and any amino acid residue located from a position equivalent to position 17 to a position equivalent to position 25 of SEQ ID NO: 2, after optimal global alignment with SEQ ID NO:2.

The invention discloses an HSP70-targeting chimeric antigen receptor-macrophage and application thereof in treatment of noise-induced hearing loss, an extracellular domain of the HSP70-targeting chimeric antigen receptor comprises an HSP70 specific binding fragment, an intracellular domain comprises an IL-4 signal channel functional element, a signal switch type CAR structure of the HSP70 is formed, and the macrophage can be used for treating noise-induced hearing loss, so that the HSP70-targeting chimeric antigen receptor-macrophage can be used for treating noise-induced hearing loss. The HSP70-targeted chimeric antigen receptor-macrophage can be used for preparing the HSP70-targeted chimeric antigen receptor-macrophage, is used for mediating polarization of the macrophage to an M2 type and exerting an anti-inflammatory function, is proved to be capable of specifically responding to an inner ear inflammation microenvironment, switching an anti-inflammatory phenotype and protecting hair cells and auditory nerves, can be used for treating noise-induced hearing loss, and can be used for preparing the HSP70-targeted chimeric antigen receptor-macrophage. The limitation that traditional hearing-aid equipment supports treatment on symptoms is broken through, and the hearing-aid device has a remarkable application prospect.

The invention discloses a neutralizing antibody with an AQP3 channel blocking function as well as a preparation method and application thereof, and belongs to the technical field of biological medicines. The neutralizing antibody can be specifically combined with an extracellular domain of AQP3, after combination, a water channel and a small molecule transport function of the AQP3 are blocked through steric hindrance and conformation change, and meanwhile, antigen combination specificity is reserved. The preparation method is realized through'recombinant antigen-immunization-B cell screening culture-recombinant antibody expression and affinity purification-ELISA detection ', and the functions of the antibody are ensured. The antibody can be efficiently combined with AQP3 positive cells, is strong in targeting property and high in specificity (the serum titer reaches 1: 1024 * 10, and the purified antibody titer is greater than or equal to 1: 128 * 10), and can be independently used or combined with a nano-carrier for treating related diseases, so that the technical bottleneck that a common AQP3 antibody can only be combined and cannot efficiently play a blocking role is solved.

Provided herein are bispecific antigen-binding molecules that bind HER2 and methods of use thereof. The bispecific antigen-binding molecules comprise a first and a second antigen-binding domain, wherein the first and second antigen-binding domains bind to two different (preferably nonoverlapping) epitopes of the extracellular domain of human HER2. The bispecific antigen-binding molecules cluster on the surface of HER2 IHC2+ and IHC3+ cells, and are internalized into the cellular lysosomes. Also included are antibody-drug conjugates (ADCs) comprising the antibodies or bispecific antigen-binding molecules provided herein linked to a cytotoxic agent, radionuclide, or other moiety, as well as methods of treating cancer in a subject by administering to the subject a bispecific antigen-binding molecule or an ADC thereof.

The invention relates to the field of biological medicine. Specifically, the invention relates to an isolated protein, and the isolated protein is a variant protein of a VZV gE extracellular domain. The invention also relates to nucleic acid molecules encoding the isolated proteins, vectors, host cells, engineered VZV viruses comprising the isolated proteins, compositions, and their use for the prevention and / or treatment of conditions caused by VZV infection.

The present disclosure relates to antibodies that bind the extracellular domain of human TREM2 and the use of anti-TREM2 antibodies in therapy, prophylaxis, diagnosis, screening, and monitoring, including for increasing levels of soluble TREM2 (sTREM2) in serum and brain, increasing phagocytosis by microglia and / or macrophages, and developing treatments to address TREM2-mediated conditions that may benefit from enhanced phagocytosis by microglia and / or macrophages.

The present application relates to the technical fields of biological medicine and cellular immunotherapy, and particularly relates to a signal conversion receptor targeting IL-10, an engineered macrophage and application thereof. The signal conversion receptor is composed of an extracellular domain and a transmembrane domain and an intracellular domain derived from TLR9, and the extracellular domain sequentially comprises a signal peptide, a HA tag and a specific binding domain of an IL-10 receptor alpha subunit from N-terminal to C-terminal. The present application further prepares an engineered macrophage SR CAR-M capable of specifically recognizing IL-10 and converting it into a TLR9 activation signal, which can induce macrophages to polarize to M1 type and has excellent phagocytosis and killing capacity for bladder cancer, breast cancer, lung cancer and melanoma cells, and can be used for preparing related tumor treatment drugs, overcoming the common problems of existing cell therapy, such as easy exhaustion, difficult infiltration and easy inhibition in solid tumors, and having significant clinical transformation potential.

Mice that comprise a replacement of endogenous mouse IL-6 and / or IL-6 receptor genes are described, and methods for making and using the mice. Mice comprising a replacement at an endogenous IL-6Rα locus of mouse ectodomain-encoding sequence with human ectodomain-encoding sequence is provided. Mice comprising a human IL-6 gene under control of mouse IL-6 regulatory elements is also provided, including mice that have a replacement of mouse IL-6-encoding sequence with human IL-6-encoding sequence at an endogenous mouse IL-6 locus.

The present invention provides a fusion protein for activating an immune cell to kill a tumor cell, and a recombinant virus and a use thereof. The fusion protein comprises an extracellular domain, a hinge region, a transmembrane domain, and an intracellular domain, wherein the extracellular domain is a polypeptide or an active fragment thereof that specifically binds to an immune cell surface antigen, and a killing function of the immune cell is activated by specifically binding to the immune cell surface antigen; and the transmembrane domain is a polypeptide for anchoring the fusion protein on a cell membrane of the tumor cell. The fusion protein and recombinant virus of the present invention can effectively kill the tumor cell and have broad-spectrum killing activity against various tumors.

The invention provides a chimeric antigen receptor targeting CD19 and / or CD20 and application thereof, the chimeric antigen receptor comprises: an extracellular domain capable of binding to CD20 and / or CD19; the extracellular domain is connected with the amino acid sequence, the transmembrane domain is connected with the extracellular domain, the intracellular domain is connected with the transmembrane domain, and the intracellular domain is selected from all amino acid sequences or partial amino acid sequences of at least one of the following proteins: 2B4, DAP10 and CD3zeta. The chimeric antigen receptor disclosed by the invention has double-target recognition capability and can be simultaneously combined with CD19 and CD20, so that the chimeric antigen receptor can cover a full differentiation stage of pathogenic B cells in autoimmune diseases and block a production path of an autoantibody from a source of a pathological mechanism; meanwhile, based on the inherent regulation and control capability of NK cells on lesion T cells, pathogenic T cells are removed, and the removal effect of B cells is cooperated, so that bidirectional blocking treatment on autoimmune pathology is realized.

Disclosed herein are methods and compositions of RANKL-binding switch receptors and engineered immune cell comprising said switch receptors, wherein the switch receptor comprises a RANKL-binding ectodomain, transmembrane domain and a costimulatory endodomain.

This provides a gp130 binding molecule. [Solution] This disclosure provides a biologically active molecule comprising a single-domain antibody (sdAb) that specifically binds to the extracellular domain of human gp130, a composition comprising such an antibody, and a method of using the same.

This invention discloses monoclonal antibodies that recognize linear B-cell epitopes in the conserved extracellular domain of pseudorabies virus (PRV) gE protein and their applications. Using recombinant PRV gE protein extracellular domain protein as an immunogen, hybridoma cell lines were prepared. Combining dot blot and peptide scanning techniques, two monoclonal antibodies, 4E5D7 and 8F6B2, were screened to recognize the 69-93aa region of the conserved extracellular domain of the PRV gE protein. Both antibodies achieved a titer of 1:2048000 and specifically recognized the native PRV wild-type gE protein, showing no cross-reactivity with gE gene-deleted vaccines. The monoclonal antibodies of this invention fill the gap in detection reagents targeting the precise epitopes of the 69-81aa and 79-93aa extracellular domains of the PRV gE protein, thus improving the linear B-cell epitope map of the PRV gE protein. These monoclonal antibodies can be used for research on the pathogenesis of PRV and the development of specific detection reagents for PRV wild-type strains, possessing significant application value and translational prospects in basic scientific research, veterinary clinical testing, and animal disease prevention and control.