112 results about "Ectodomain" patented technology

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.

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 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.

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.

The present invention relates to a viral vector capable of generating a cellular immune response against a spike (S) protein of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), characterized in that the viral vector is a Newcastle disease virus (NDV) comprising a nucleotide sequence of SEQ ID NO: 6 or SEQ ID NO: 14 and an exogenous nucleotide sequence encoding antigenic sites of SARS-CoV-2, wherein the exogenous nucleotide sequence comprises a sequence having at least 95% sequence identity with a sequence that translates into the amino acid sequence of SEQ ID NO: 11, wherein the exogenous nucleotide sequence comprises an ectodomain of a SARS-CoV-2 S protein fused with a transmembrane domain and a cytoplasmic domain of an NDV fusion (F) protein, wherein the polybasic cleavage site of the ectodomain of the S protein is mutated to alanine and amino acids 817, 892, 899, 942,986 and 987 of the ectodomain of the S protein of SEQ ID NO: 11 are prolines, such that the viral vector and antigenic sites are stable after at least 3 consecutive passages in chicken embryo.

The present disclosure provides a population of genetically modified immune cells and uses thereof, the modified immune cells comprising (i) a chimeric antigen receptor (CAR) targeting a target protein on a target cell; (ii) a first immunomodulatory fusion protein comprising an ectodomain derived from a protein of tumor necrosis factor (TNF) superfamily, and an endodomain derived from a costimulatory molecule of a TNF receptor superfamily protein; (iii) a second immunomodulatory fusion protein comprising an ectodomain derived from a protein of TNF receptor superfamily, and an endodomain derived from a common g-chain cytokine receptor; and (iv) a third immunomodulatory fusion protein comprising an ectodomain derived from the same TNF receptor superfamily protein as in the second immunomodulatory fusion protein, and an endodomain derived from an a or b receptor subunit of the common g-chain cytokine receptor family.

Embodiments of a recombinant Respiratory Syncytial Virus (RSV) F ectodomain trimer stabilized in a prefusion conformation are provided. Also disclosed are nucleic acids encoding the RSV F ectodomain trimer and methods of producing the RSV F ectodomain trimer. Methods for inducing an immune response in a subject are also disclosed. In some embodiments, the method can be a method for treating or preventing a RSV infection in a subject by administering a therapeutically effective amount of the recombinant RSV F ectodomain trimer to the subject.

The invention discloses a PD-L1 cell targeting fusion protein connected in series with a TGFBR2 extracellular domain, IL-2 and a receptor thereof, and an application thereof. Belongs to the technical field of biology. The fusion protein provided by the invention is a heterotetramer formed by connecting two similar heavy polypeptide chains and two similar light polypeptide chains through a disulfide bond. The fusion protein realizes triple functions through a single molecule: tumor specific localization is realized through PD-L1 targeting VHH (Vascular Haemophilus Haemophilus Haemophilus Haemophilus Haemophilus Haemophilus Haemophilus Haemophilus Haemophilus Haemophilus Haemophilus); an immunosuppressive factor TGF-beta in a tumor microenvironment is neutralized through TGFBR2 ECD; effect immune cells expressing a medium affinity IL-2 receptor are selectively activated and amplified by the combination of IL-2 and IL-2R alpha. The PD-L1 inhibitor provided by the invention overcomes the multiple problems of limited curative effect of a single drug, high IL-2 systemic toxicity, tumor microenvironment immunosuppression and the like in the existing PD-(L) 1 inhibitor, and provides technical support for detection, prevention and treatment of PD-L1 positive tumors.

The present invention relates to a gene cassette expressing a fusion protein, a method for constructing same, and a method for detecting a target ligand, using same. When a target ligand binds to a target receptor ectodomain to form a dimer, a fused split fluorescent protein fragment is assembled to generate a fluorescence signal, thereby enabling rapid and simple monitoring of the presence or absence of the target ligand.

The invention provides a chimeric autoantibody receptor of a targeted acetylcholine receptor antibody, a CAAR-T cell and application of the chimeric autoantibody receptor in a medicine for preventing and treating myasthenia gravis, and belongs to the technical field of biological medicines. The invention provides a chimeric autoantibody receptor (CAAR) targeting an acetylcholine receptor antibody, which is characterized in that three extracellular domains of an AChR alpha subunit are connected in series through L1 and L2 connecting peptides or G4S connecting peptides to form an extracellular domain, and meanwhile, CD3 gamma only containing an ITAM motif is used as a signal transduction domain. The CAAR is expressed on the surface of a T cell, and the obtained CAAR-T not only has relatively strong binding capacity with an anti-AChR antibody, shows a relatively strong killing effect on pathogenic B cells expressing the anti-AChR antibody, can effectively relieve the symptom of myasthenia gravis, but also has relatively low risk of inducing cytokine storm, and has good drug safety.

The present application relates to the field of immunological detection, and particularly relates to a reagent for detecting varicella-zoster virus infection and a preparation method thereof. The reagent comprises R1 reagent and R2 reagent; the R1 reagent is a working solution of streptavidin magnetic beads, and the preparation method comprises the following steps: firstly coupling activated carboxyl magnetic beads with streptavidin; dialyzing the magnetic beads obtained by the first coupling to remove streptavidin physically combined with the magnetic beads; secondly coupling the dialyzed magnetic beads with streptavidin; quenching the magnetic beads obtained by the second coupling, and then placing the magnetic beads in a working solution to obtain the working solution; the working solution contains fetal bovine serum, bovine serum albumin and lysine; the R2 reagent is a biotinylated VZV gE recombinant protein, and the VZV gE recombinant protein is a varicella-zoster virus gE glycoprotein extracellular domain fragment expressed by human embryonic kidney cells. The reagent has high sensitivity and specificity in the detection of varicella-zoster virus infection.