254 results about "Ectodomain" patented technology

The invention belongs to the technical field of vaccines and biology, and particularly relates to a broad-spectrum influenza A vaccine immunogen composition and application. The invention provides a nucleic acid molecule for coding an immunogenic peptide, wherein the immunogenic peptide comprises: M2 protein extracellular region (M2e) peptide fragments which are connected in series; a hemagglutinin protein stem region extracellular domain (HA2) peptide fragment derived from an H7N9 influenza virus subtype; multimerization of the motif peptide fragment; and optionally, one or more linker peptide fragments independently located between the peptide fragments, wherein the polynucleotide molecule comprises a coding nucleic acid of each peptide fragment. The broad-spectrum influenza A vaccine can induce an organism to generate antigen-specific immune response, a high-titer antibody can be generated 14 days after last inoculation, the broad-spectrum influenza A vaccine can completely protect and resist attack of various subtype influenza A viruses, and the broad-spectrum influenza A vaccine has a wide application prospect.

The invention relates to the technical field of biological medicines, in particular to a rabies virus G protein mutant as well as a preparation method and application thereof. The rabies virus G protein mutant is obtained by carrying out point mutation on an extracellular domain of G protein, the mutant realizes soluble expression of the extracellular domain of the G protein, can induce generation of a high-titer neutralizing antibody, and has more excellent cellular immunity and antibody immune response compared with commercial human rabies vaccines and canine rabies vaccines; the inoculation frequency is expected to be reduced, the immune procedure is shortened, and the immune dosage is reduced.

There are provided polypeptides that include an Activin receptor type IIB (ActRIIB) ectodomain (ECD) variant. In some embodiments, a polypeptide of the disclosure includes an ActRIIB-ECD variant fused to an Fc domain moiety. The disclosure also provides pharmaceutical compositions and methods of using the polypeptides to treat diseases and conditions associated with TGFβ 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 (such as anemia).

There are provided polypeptides that include an Activin receptor type IIB (ActRIIB) ectodomain (ECD) variant. In some embodiments, a polypeptide of the disclosure includes an ActRIIB-ECD variant fused to an Fc domain moiety. The disclosure also provides pharmaceutical compositions and methods of using the polypeptides to treat diseases and conditions associated with TGFβ superfamily ligand signaling, such as pulmonary hypertension, fibrosis, muscle weakness and atrophy, metabolic disorders and / or cardiometabolic disease, bone damage, and / or low red blood cell levels (such as anemia).

The invention provides a novel three-antigen HSV-2 adjuvant subunit vaccine as well as a preparation method and application thereof. The vaccine comprises herpes simplex virus recombinant protein and a composite adjuvant, the herpes simplex virus recombinant protein comprises extracellular domains of three proteins, namely HSV-2gE, gD and gC, wherein the amino acid sequences of the extracellular domains of the HSV-2gE, the gD and the gC are respectively shown as SEQ ID NO.1, SEQ ID NO.2 and SEQ ID NO.3; and the composite adjuvant is composed of CpG oligodeoxynucleotide and QS-21. Experiments prove that by adding the composite adjuvant composed of CpG oligodeoxynucleotide and QS-21, the immunogenicity, in-vivo protectiveness, virus removal and other immune functions of the HSV-2 subunit vaccine can be remarkably improved; meanwhile, the vaccine is a cross immune protection vaccine of an HSV-2 virus strain and an HSV-1 virus strain.

The invention relates to the technical field of biomedicine, in particular to a fusion protein combining a double-target chimeric antigen receptor with PD-1 and IL-21, and an extracellular domain of the double-target chimeric antigen receptor sequentially comprises any one of the following components from an N terminal to a C terminal: CIgG scFv-MSLN scFv, CIgG scFv-CLDN18.2 scFv, CIgG scFv-MSLN scFv and CIgG scFv-CLDN18.2 scFv; wherein '-' is a connecting peptide; the cell further comprises a hinge region, a transmembrane region and an intracellular signal transduction region; pD-1 scFv and IL-21 are further fused at the N end of the intracellular signal transduction region. According to the invention, two chimeric antigen receptors of double-target combined PD-1 and IL21 fusion proteins are constructed, and through a synergistic anti-tumor strategy, CAR-T cell functions are enhanced, tumor microenvironment (TME) inhibition is overcome, T cell durability is improved, and synergy is realized.

The present disclosure provides a polyribonucleotide encoding a polypeptide that comprises a viral antigen from Herpes Simplex Virus-2 (HSV-2); for example, the viral antigen comprises the ectodomain of HSV-2 glycoprotein B. The polyribonucleotide can be formulated as an RNA composition useful for inducing anti-HSV immune responses in a subject.

The present disclosure provides compositions and methods for targeting neoantigens, for example, to treat or prevent cancer. The disclosed embodiments include binding proteins, such as T cell receptors, that bind to the neoantigen: HLA complex. The binding protein further comprises a construct comprising a fusion protein of the CD95 extracellular domain and the CD137 intracellular signaling domain (Fas-41BB), and a CDS coreceptor alpha or beta chain. The disclosed binding proteins are highly sensitive to antigens and are capable of inducing activation of host T cells at low concentrations of peptide antigens. In certain embodiments, binding proteins of the present disclosure (i) have no alloreactivity, substantially no alloreactivity, and / or low risk of alloreactivity, to amino acid sequences from human proteomes and / or (ii) to human HLA alleles. Polynucleotides encoding such binding proteins can be introduced into host cells, such as T cells, and the cells can be used in immunotherapy for the treatment of various cancers.

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 present invention discloses an antibody targeting prostate-specific membrane antigen, an antigen-binding fragment thereof, a preparation method and uses thereof. In the antibody or its antigen-binding fragment, the amino acid sequences of HCDR1, HCDR2 and HCDR3 are respectively as shown in SEQ ID NO:4, SEQ ID NO:5 and SEQ ID NO:6; and / or, the amino acid sequences of LCDR1, LCDR2 and LCDR3 are respectively as shown in SEQ ID NO:7, SEQ ID NO:8 and SEQ ID NO:9. The antibody can specifically bind to the extracellular domain protein of human and monkey PSMA, can effectively bind to C4-2 and 22RV1 cells, and the ADC containing the same can effectively kill tumor cell lines.

The present invention relates to the technical field of biomedicine. Provided are a rabies virus G protein mutant, and a preparation method therefor and the use thereof. The rabies virus G protein mutant is obtained by means of a site mutation on the extracellular domain of a G protein. For the mutant, soluble expression of the extracellular domain of the G protein is realized, and the mutant can induce the generation of a neutralizing antibody with a high titer. Compared with commercial rabies vaccines for human and rabies vaccines for dogs, the mutant has better cell immune and antibody immune responses. The mutant is expected to reduce the inoculation frequency, shorten the immunizing procedure, and decrease the immunizing dose.

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.

Provided are a chimeric antigen receptor, and a GPRC5D antibody-containing chimeric antigen receptor and a use thereof. The chimeric antigen receptor comprises: an extracellular domain, wherein the extracellular domain is capable of binding to a tumor antigen; a transmembrane domain, wherein the transmembrane domain is connected to the extracellular domain, and the transmembrane domain is derived from an I-type transmembrane protein or an artificially synthesized transmembrane protein having a hydrophobic helix; and an intracellular domain, wherein the intracellular domain is connected to the transmembrane domain, and the tumor antigen is a tumor-specific antigen or a tumor-associated antigen. The amino acid sequence of the transmembrane domain is optimized, thereby providing a GPRC5D antibody-containing chimeric antigen receptor and engineered immune cells; and the engineered immune cells obtained on the basis of the GPRC5D antibody have specific killing performance on multiple myeloma.

The invention relates to the technical field of biology, in particular to a chimeric antigen receptor of a specific targeting tumor non-classical HLA molecule, polynucleotide, an expression vector, a recombinant virus, a recombinant cell, a composition and pharmaceutical application. An extracellular domain of the chimeric antigen receptor specifically combined with the HLA-G in a targeted manner is an antigen binding structural domain of an ILT2 receptor, and compared with a CAR modified immune cell with an antigen binding region of an antibody as an extracellular domain, the HLA-G targeted immune response cell provided by the invention can recognize numerous tumor cells in a broad-spectrum manner on one hand, so that the HLA-G targeted immune response cell can be used for preparing an HLA-G targeted immune response cell; the killing efficiency and accuracy of various tumor cells are greatly improved; and on the other hand, the extracellular domain is an antigen binding domain of an ILT2 receptor, and the binding domain is a binding domain of a natural receptor, so that compared with an artificially synthesized antibody, the antigen binding domain is safe and reliable, and can truly reflect the target binding capacity in a natural state.

The invention relates to the technical field of biology, in particular to a chimeric antigen receptor, a chimeric antigen receptor containing a GPRC5D antibody and application of the chimeric antigen receptor, and the chimeric antigen receptor comprises an extracellular domain which can be combined with a tumor antigen, an inflammatory factor or a pathogen antigen; the transmembrane domain is connected with the extracellular domain, and the transmembrane domain is derived from a type I transmembrane protein or an artificially synthesized transmembrane protein with a hydrophobic helix; the intracellular domain is connected with the transmembrane domain, and the tumor antigen is a tumor specific antigen or a tumor associated antigen. The inventor optimizes the amino acid sequence of the transmembrane domain, so that the chimeric antigen receptor containing the GPRC5D antibody and the engineered immune cell are provided, and the engineered immune cell obtained based on the GPRC5D antibody has specific killing performance on multiple myeloma.

In one aspect, provided herein is a mosaic influenza virus hemagglutinin (HA) polypeptide comprising an influenza A virus HA ectodomain of an influenza A virus strain HA, wherein the HA ectodomain comprises an HA stem domain of the influenza A virus strain HA and an HA globular head domain of the influenza A virus strain HA, wherein the HA globular head domain of the influenza A virus strain HA has been engineered to comprise one or more amino acid substitutions in one, two, three, four or all of the antigenic sites. In another aspect, provided herein are immunogenic compositions comprising such a mosaic influenza virus HA polypeptide or an influenza A virus comprising such a mosaic influenza virus HA polypeptide. In yet another aspect, provided herein are methods for immunizing a subject against an influenza A virus in a subject comprising administering such an immunogenic composition to the subject.

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.

Provided herein are recombinant polypeptides comprising an engineered ectodomain of a viral protein from enveloped viruses. Also provided herein ar two-component protein nanostructures and compositions for use in vaccinating, generating an immune response, or treating or preventing a viral infection.

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.

Provided are virus-like particle vaccines for human metapneumovirus (hMPV) in which the ectodomain of hMPV F protein is linked to, and thereby displayed on, a symmetric protein-based virus-like particle. For example, the vaccine antigen may be a N-terminal fusion of the ectodomain of hMPV F protein to a protein having a multimerization domain for a one- or two-component virus-like particle, such as a two-component icosahedral virus-like particle. Further provided are vaccine compositions, methods of manufacturing, and methods of use, e.g., immunizing a subject to generate a protective immune response to hMPV.

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 discloses an antibody targeting a prostate specific membrane antigen, an antigen binding fragment thereof, a preparation method and application thereof. In the antibody or the antigen binding fragment thereof, the amino acid sequences of HCDR1, HCDR2 and HCDR3 are respectively as shown in SEQ ID NO: 4, SEQ ID NO: 5 and SEQ ID NO: 6; and / or the amino acid sequences of the LCDR1, the LCDR2 and the LCDR3 are respectively shown as SEQ ID NO: 7, SEQ ID NO: 8 and SEQ ID NO: 9. The antibody can be specifically combined with PSMA extracellular domain proteins of human and monkeys and can be effectively combined with C4-2 and 22RV1 cells, and ADC containing the antibody can effectively kill tumor cell lines.

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.