40 results about "CD8A" patented technology

The invention belongs to the technical field of tumor micro-immune environments, and particularly relates to a kit for detecting a tumor micro-environment, a detection method and application, the kit comprises rare metal element labeled monoclonal antibodies, the rare metal element labeled monoclonal antibodies comprise 115In-CD20, 139La-Histone H3, 142Nd-CD56, 144Nd-CD14, 146Nd-Vimentin, 148Nd-Pan-CK, 151Eu-CD31, 156Gd-CD4, 158Gd-E-Cadrin, 159Tb-CD68, 162Dy-CD8a, 166Er-CD45, 167Er-CD15, 170Er-CD3, 171Yb-CD11c and 209Bi-alpha-SMA, and the rare metal element labeled monoclonal antibodies comprise The invention can be used for simultaneously detecting and researching the quantity, positioning and spatial topological relation of each cell component in a tumor microenvironment, and provides a multi-immunofluorescence detection kit and method for ubiquitous epithelial differentiation-derived tumors based on an imaging mass spectrum flow technique. A plurality of biomarkers can be analyzed at the same time by using multiple immunohistochemical staining and rare earth metal tag signal detection technologies, so that the aim of performing high-dimensional analysis on a tumor microenvironment is fulfilled according to cell composition, functional state and cell-cell space interaction relationship.

To provide a biomarker for clonal hematopoiesis.SOLUTION: The present inventors have found that PYY, LEP, SCN3A, FCGR2A, CYTH3, CD8A, TK1, GBP6, DSC2, GP5, IL17D, CD244, SLC4A1, BGN, APOA4, and MMP7 in a body fluid sample are biomarkers for clonal hematopoiesis.SELECTED DRAWING: None

The invention discloses a recombinant protein for detecting a para-tumor Yo antibody through a CBA method and application, and belongs to the technical field of biomedical engineering.The amino acid sequence of the recombinant protein sequentially comprises a secretory signal peptide, a CDR2 protein partial sequence, a CDR2L protein partial sequence, a transmembrane region and a fluorescent label, and the secretory signal peptide is human albumin signal peptide ALB; the transmembrane region is a CD8a hinge; and the fluorescent label is mCherry. A novel recombinant protein which can be stably over-expressed on a cell membrane of an eukaryotic cell is constructed by intercepting specific partial sequences of CDR2 protein and CDR2L protein and redesigning and fusing a fluorescent label by using a secretory signal peptide, a transmembrane sequence and a connecting peptide, and the recombinant protein retains respective core antigen regions of the CDR2 protein and the CDR2L protein, so that the specific partial sequences of the CDR2 protein and the CDR2L protein can be stably over-expressed on the cell membrane of the eukaryotic cell. The kit can effectively overcome the defects in the aspects of sensitivity and specificity, and when a CBA method is adopted for detection, the detection rate of the para-tumor Yo antibody can be remarkably increased, and the false positive rate is reduced, so that the requirements of clinical detection are better met.

The disclosure provides a method for treating a subject afflicted with a tumor comprising administering to the subject a therapeutically effective amount of an anti-PD-1 antibody or antigen-binding portion thereof or an anti-PD-L1 antibody or anti-gen-binding portion thereof, wherein the subject is identified as having a high inflammatory gene signature score. In some embodiments, the high inflammatory gene signature score is determined by measuring the expression of a panel of inflammatory genes in a tumor sample obtained from the subject, wherein the inflammatory gene panel comprises CD274 (PD-LI), CD8A, LAG3, and STAT1.

Disclosed are methods of predicting a. subject's responsiveness to an immunotherapy comprising detecting the presence and / or amount of a miR155 gene signature in the subject or a sample from the subject, wherein the miR155 gene signature comprises one or more of miR155, CD3E, CD3G, CD8A, CD8B, CXCR6, FXYD5, GZMB, ID2, IFNgamma, LAGS, NKG7, PDCD1, S100A4, and TIGIT; and comparing the presence and / or amount of the miR155 gene signature to a control sample or threshold, wherein the presence and / or an altered amount of the miR155 gene signature relative to the presence or amount in the control sample or threshold indicates the subject will be responsive or is responding to the immunotherapy.

The disclosure provides binding agents that specifically bind to CD8 (e.g., antibodies or their antigen-binding fragments, binding proteins), and their use in the treatment of diseases or disorders such as inflammatory diseases or autoimmune diseases. In some embodiments, the disclosure provides binding domains and binding proteins that target CD8a. In some embodiments, the disclosure provides binding proteins comprising (a) a light chain variable region (VL) having at least 90% identity with the amino acid sequence of SEQ ID NO: 133 (wherein X=G or C), and (b) a heavy chain variable region (VH) having at least 90% identity with the amino acid sequence of SEQ ID NO: 144 (wherein (1) X1=I or F, (2) X2=G or C, (3) X3=F or V, (4) X4=A or F, (5) X5=A or R, and X6=G or A).

The application discloses a marker combination for predicting the curative effect of liposarcoma based on immunohistochemistry, a screening method and a prediction model thereof and a construction method thereof. The application analyzes the tissue phenotype characteristics of a liposarcoma patient by using an immunohistochemistry technology, combines transcriptomic data, screens a suitable marker combination NCF1, CD27, LST1, CD8A and AOAH based on Lasso-logistic regression, and establishes a more accurate immunotherapy curative effect prediction model for the liposarcoma patient.

Provided is a biomarker for clonal hematopoiesis. PYY, LEP, SCN3A, FCGR2A, CYTH3, CD8A, TK1, GBP6, DSC2, GP5, IL17D, CD244, SLC4A1, BGN, APOA4, and MMP7 in a body fluid sample.

This disclosure provides a method for treating a cancer patient comprising administering to the patient a therapeutically effective amount of an anti-PD-1 antagonist, for example, an anti-PD-1 or anti-PD-L1 antibody, in combination with an indolamine 2,3-dioxygenase inhibitor, wherein the patient is identified as exhibiting a combined biomarker comprising (a) a high IFNγ inflammatory signature score and (b) a low tryptophan 2,3-dioxygenase 2 (TDO2) gene expression score. The high IFNγ inflammatory signature score is determined by measuring the expression of a panel of IFNγ-related inflammatory genes in a cancer sample obtained from the patient, wherein the gene panel comprises, for example, IFNγ, CXCL10, CXCL9, HLA-DRA, IDO1, and STAT1. In some respects, the gene panel also includes CCR5, CXCL11, GZMA, and PRF1.In some aspects, the genetic panel comprises CXCR6, TIGIT, PD-L1, PD-L2, LAG3, NKG7, PSMB10, CMKLR1, CD8A, IDO1, CCL5, CXCL9, HLA.DQA1, CD276, HLA.DRB1, STAT1, HLA.E and TDO2.

The invention relates to the technical field of biological medicine, and particularly discloses a chimeric antigen receptor of a targeted NKG2D ligand, a nucleic acid molecule, an expression vector, a macrophage and a preparation method and application of the chimeric antigen receptor, the nucleic acid molecule, the expression vector and the macrophage, and an extracellular antigen binding domain is an NKG2D extracellular structural domain; the hinge region is a CD28 hinge region or a CD8a hinge region; the transmembrane / intracellular signal transduction structural domain is an FCGR1 transmembrane / intracellular signal transduction structural domain or a CD3z transmembrane / intracellular signal transduction structural domain. The chimeric antigen receptor provided by the invention specifically recognizes and is combined with NKG2DLs highly expressed in NKG2DL positive malignant tumors, and macrophages expressing the chimeric antigen receptor can directly swallow tumor cells, promote M1 type polarization, reprogram tumor microenvironment and induce recruitment and activation of T cells, so that effective treatment of the malignant tumors is realized.

The invention discloses an application of a TNFRSF12A inhibitor in preparation of a medicine for treating oral squamous cell carcinoma. Based on single cell transcriptome data, oral squamous cell canceration related tissues are divided into four tissue ecological subtypes, and a tumor sample is divided into two subtypes ET3 and ET4. The ET3 subtype is a lymphocyte infiltration type, and shows CD8 + T cell infiltration, immune activation pathway activity enhancement and high expression of CD3, CD8A and PDCD1; the ET4 subtype is a lymphocyte rejection type, is enriched with COL1A1 + fibroblasts, and is accompanied by high expression of TNFRSF12A, COL1A1 and CD276. According to the application disclosed by the invention, the expression of the TNFRSF12A in the ET4 subtype is obviously improved, in-vivo experiments prove that knockout or blocking of the TNFRSF12A can promote lymphatic T cell infiltration and inhibit tumor growth, and a stronger inhibition effect is shown when the knockout or blocking of the TNFRSF12A is combined with an immune checkpoint inhibitor. The invention provides a system for typing oral squamous cell carcinoma.

The disclosure provides a method for treating a subject afflicted with a cancer comprising administering to the subject a therapeutically effective amount of an anti-PD-1 antagonist, e.g., an anti-PD-1 or anti-PD-L1 antibody, in combination with an indoleamine 2,3-dioxygenase inhibitor, wherein the subject is identified as exhibiting a combined biomarker comprising (a) a high IFNγ inflammatory signature score and (b) a low tryptophan 2,3-dioxygenase 2 (TDO2) gene expression score. The high IFNγ inflammatory signature score is determined by measuring the expression of a panel of IFNγ related inflammatory genes in a cancer sample obtained from the subject, wherein the gene panel comprises, e.g., IFNγ, CXCL10, CXCL9, HLA-DRA, IDO1, and STAT1. In some aspects, the gene panel further comprises CCR5, CXCL11, GZMA, and PRF1. In some aspects, the gene panel comprises CXCR6, TIGIT, PD-L1, PD-L2, LAG3, NKG7, PSMB10, CMKLR1, CD8A, IDO1, CCL5, CXCL9, HLA.DQA1, CD276, HLA.DRB1, STAT1, HLA.E, and TDO2.

Novel anti-CD8α (cluster of differentiation 8 alpha) antibodies and antigen-binding fragments thereof, a fusion protein including the anti-CD8α antibodies and antigen-binding fragments thereof, and a nucleic acid molecule encoding the anti-CD8α antibodies and antigen-binding fragments thereof. Also, pharmaceutical compositions including the anti-CD8α antibodies and antigen-binding fragments thereof. Further, methods using the anti-CD8α antibodies and antigen-binding fragments thereof for treating CD8-related diseases and in vitro methods in which CD8a-expressing cells are depleted in a sample or in which CD8α is detected or quantified in a sample.

The present invention relates to genetically engineered NK cells and uses thereof. Specifically provided is a host cell comprising a nucleic acid construct comprising (1) a nucleotide sequence encoding a TCR and a CD8a molecule and (2) a nucleotide sequence encoding a CD3 molecule. The cells produced by the present invention have significant cytotoxicity against specific tumor cells and retain the killing effect of NK cells on tumor cells with down-regulated MHC class I molecules.

The current disclosure provides methods and compositions that provide for the insertion of transgenes in stem or progenitor cells without the deleterious effects to T cell differentiation by in vitro T cell differentiation methods. To accomplish this, the inventors have discovered that expression of the transgenes under the control of promoter regions, such as CD8a or CD8b, allows for the coordinated expression pattern that provides for both: 1) high expression of the transgene in mature T cells and 2) a coordinated level of expression of the transgene throughout the in vitro differentiation method that allows for the production of a population of mature T cells.

Provided herein are methods of treating chronic viral infection (e.g., hepatitis B virus (HBV) and / or human immunodeficiency virus (HIV) infection), comprising administering to an individual in need thereof an effective amount of a fusion protein comprising: (a) a first portion comprising an antibody or antigen-binding fragment thereof, the antibody or antigen-binding fragment thereof specifically binds to human CD8b and / or human CD8ab with an affinity at least 10 times higher than its binding to human CD8a and / or human CD8aa; and (b) a second portion comprising a cytokine, a chemokine, or a growth factor.

The invention discloses an antibody combination suitable for detecting DLBCL immune microenvironment by an imaging mass spectrometer, a kit and application. The antibody combination is an antibody for resisting alpha SMA, an antibody for resisting HLADR, an antibody for resisting CD20, an antibody for resisting CD56, an antibody for resisting Vimentin, an antibody for resisting CD8a, an antibody for resisting CCL17, an antibody for resisting CCR6, an antibody for resisting IL3CD123, an antibody for resisting CXCL12, an antibody for resisting BCL2, an antibody for resisting PD1, an antibody for resisting CD163, an antibody for resisting CD45RO, an antibody for resisting ICOS, an antibody for resisting GranzymeB, an antibody for resisting CXCR5, an antibody for resisting Ki67, an antibody for resisting PDL1, an antibody for resisting Bcl6, an antibody for resisting CD31, an antibody for resisting CD163, an antibody for resisting CD45RO, an antibody for resisting CD27, an And all the antibodies are marked. The DLBCL immune microenvironment can be more comprehensively and efficiently identified by using the antibody combination disclosed by the invention.

Fibronectin type III domains (FN3) that specifically bind to CD8A, related polynucleotides capable of encoding CD8A-specific FN3 domains, cells expressing the FN3 domains, as well as associated vectors, and detectably labeled FN3 domains are useful in therapeutic and diagnostic applications.

The present disclosure is directed to synthetic receptor molecules comprising truncated versions of HER2 and CD8a for use in methods for enriching, tracking and / or eliminating genetically modified cells, including those used in cellular therapies.

A method for treating cancer in a patient who is identified as a good responder to antitumoral treatment, who presents an elevated expression level of at least one gene representative of immune adaptative responses (e.g., CD8A) and an elevated expression level of at least one gene representative of immunosuppressive responses (e.g., CD274).

The present invention relates to a method for predicting the survival time of a patient suffering from a solid cancer comprising i) determining in a tumor sample obtained from the patient the gene expression level of at least 7 genes selected from the group consisting of CCR2, CD3D, CD3E, CD3G, CD8A, CXCL10, CXCL11, GZMA, GZMB, GZMK, GZMM, IL15, IRF1, PRF1, STAT1, CD69, ICOS, CXCR3, STAT4, CCL2, and TBX21, ii) comparing every expression level determined at step i) with their predetermined reference value and iii) providing a good prognosis when all expression levels determined at step i) are higher than their predetermined reference values, or providing a bad prognosis when all expression levels determined at step i) are lower than their predetermined reference values or providing an intermediate prognosis when at least one expression level determined value is higher than its predetermined value. The method is also particularly suitable for predicting the responsiveness of the patient to a treatment.

The invention relates to the technical field of biological medicine, and provides a mouse anti-human CD8a recombinant monoclonal antibody and application thereof, the mouse anti-human CD8a recombinant monoclonal antibody comprises a heavy chain variable region and a light chain variable region, the heavy chain variable region comprises CDR1-VH, CDR2-VH and CDR3-VH of amino acid sequences shown as SEQ ID NO: 1-3, and FR1-VH, FR2-VH, FR3-VH and FR4-VH of amino acid sequences shown as SEQ ID NO: 4-7. Splicing to obtain a complete amino acid sequence of a heavy chain variable region of the antibody as shown in SEQ ID NO.8; the light chain variable region comprises CDR1-VL, CDR2-VL and CDR3-VL of amino acid sequences as shown in SEQ ID NO: 9 to 11, and FR1-VL, FR2-VL, FR3-VL and FR4-VL of amino acid sequences as shown in SEQ ID NO: 12 to 15. And splicing to obtain the complete amino acid sequence of the light chain variable region of the antibody as shown in SEQ ID NO.16. The heavy chain variable region and the light chain variable region are respectively connected to respective expression vectors and then co-transfect animal cells to obtain the recombinant expression CD8a recombinant antibody. The recombinant antibody disclosed by the invention has the advantages of strong specificity, high sensitivity and capability of specifically recognizing CD8a target protein in a CD8a + T cell population and a biological sample.

The invention discloses a detection reagent and a kit suitable for detecting EB (Epstein-Barr) virus positive DLBCL immune microenvironment by an imaging mass spectrometer. The detection reagent comprises an antibody combination and a probe combination, the antibody combination comprises an anti-alpha SMA antibody, an HLADR antibody, a CD20 antibody, a CD56 antibody, a Vimentin antibody, a CD8a antibody, a CCL17 antibody, a CCR6 antibody, an IL3CD123 antibody, a CXCL12 antibody, a BCL2 antibody, a PD1 antibody, a CD163 antibody, a CD45RO antibody, an ICOS antibody, a GranzymeB antibody, a CXCR5 antibody, a Ki67 antibody, a PDL1 antibody, a Bcl6 antibody, a CD31 antibody, a CD3 antibody, a CD45 antibody, a CD27 antibody, an LAG3 antibody, a PDL2 antibody, a FoxP3 antibody, a CD127 antibody, a CD4 antibody, an EBNA2 antibody, a All antibodies and probes are labeled with metal labels. The EBV + DLBCL immune microenvironment can be more comprehensively and efficiently identified by using the antibody combination or the kit disclosed by the invention.

The invention relates to a kit for screening dilated cardiomyopathy. The kit comprises a reagent for detecting one or more of genes of TP53, TNF, IL1beta, JUN, CD8A, TLR4, UBB, CTLA4, CXCL8 and NFKBIA. The kit provided by the invention is high in detection efficiency and low in detection cost, provides important reference basis for diagnosis and prognosis judgment of patients with dilated cardiomyopathy, and can remarkably improve the survival rate of the patients.

The application provides a transfer plasmid of a lentivirus, a packaging system and application in preparation of the lentivirus, CAR-T cells and a kit, and particularly relates to a lentivirus packaging system for CAR-T, which comprises a transfer plasmid, the transfer plasmid comprises a virus promoter, a CAR promoter, a coding nucleotide sequence of a CAR expression region and a virus PolyA, wherein the virus promoter is selected from RSV, the CAR promoter is selected from SFFV and EF1 alpha promoter, the hinge and transmembrane region of the CAR expression region are from CD8a or CD8b, and the virus PolyA is selected from SV40 polyA. The lentivirus packaged by the packaging system has high packaging efficiency and transduction titer, so as to meet the demand of high production of the lentivirus for CAR-T cell treatment.

Provided herein are methods of treating chronic viral infection (e.g., hepatitis B virus (HBV) and / or human immunodeficiency virus (HIV) infection) comprising administering to an individual in need thereof an effective amount of a fusion protein that comprises: (a) a first moiety comprising an antibody or antigen-binding fragment thereof that specifically binds human CD8b and / or human CD8ab with at least 10-fold higher affinity than its binding to human CD8a and / or human CD8aa; and (b) a second moiety comprising a cytokine, chemokine, or growth factor.

Novel anti-CD8α (cluster of differentiation 8 alpha) antibodies and antigen-binding fragments thereof, a fusion protein including the anti-CD8α antibodies and antigen-binding fragments thereof, and a nucleic acid molecule encoding the anti-CD8α antibodies and antigen-binding fragments thereof. Also, pharmaceutical compositions including the anti-CD8α antibodies and antigen-binding fragments thereof. Further, methods using the anti-CD8α antibodies and antigen-binding fragments thereof for treating CD8-related diseases and in vitro methods in which CD8a-expressing cells are depleted in a sample or in which CD8α is detected or quantified in a sample.

The invention discloses a group of serum protein markers for identifying systemic lupus erythematosus. The serum protein markers comprise MCP-3, ST1A1, TNF, TGF-alpha, CSF-1, AXIN1, CXCL9, IL-15RA, IL18, CCL3, IL10, 4E-BP1, PD-L1, SIRT2, CCL11, CDCP1, IL-18R1, FGF-23, CD40, STAMBP, IL6, IL-17C, CD8A, CXCL10, CXCL5, DNER, FGF-19, LAP TGF-beta-1, CCL28, CASP-8, IL8, CCL23, CCL20, CCL19, MCP-1, VEGFA, uPA, OPG, OSM, various novel protein markers which are expected to be used for screening and identifying systemic lupus erythematosus are identified.

In particular, the present invention relates to a chimeric human CD8 co-receptor wherein the CD8 co-receptor comprises a polypeptide comprising at least one functional polypeptide domain or functional polypeptide motif of a wild-type human CD8 [alpha] co-receptor, and wherein the polypeptide further comprises at least one CD8 [beta]-derived polypeptide region, the human CD8beta co-receptor comprises a functional polypeptide structural domain or a functional polypeptide motif of the wild type human CD8beta co-receptor. The invention also relates to a nucleic acid encoding the chimeric CD8 co-receptor, a vector comprising the nucleic acid encoding the chimeric human CD8 co-receptor, and an isolated T cell transduced with the nucleic acid or with the vector, and an isolated T cell transduced to express the chimeric CD8 co-receptor. The invention also relates to a kit for preparing the separated T cell provided by the invention, and a pharmaceutical composition containing the T cell. The invention also relates to a method of preparing T cells for immunotherapy and a method of treating a patient suffering from cancer comprising administering the pharmaceutical composition.

The invention discloses a chimeric antigen receptor as well as a carrier and an immune cell modified by the chimeric antigen receptor, the chimeric antigen receptor is IL2 signal-IL15-CD8a transmembrane-P2A-CD8a signal-scFv, and the chimeric antigen receptor is combined with another chimeric antigen receptor CD8a signal-GPC3 scFv-CD8a hinge-CD8a transmembrane-CD28-CD3 delta for use. The CAR modified immune cells express membrane type IL-15 and secrete and express'immune checkpoint molecule 'monoclonal antibodies. The co-expression of the cell factor IL-15 and the'immune checkpoint molecule 'monoclonal antibody not only prolongs the life cycle of the immune cells, but also prevents the inhibition signal channel of the immune checkpoint molecule by secreting and expressing the'immune checkpoint molecule' monoclonal antibody, so that the tumor cell killing effect of the immune cells is improved.