31 results about "CD8A" patented technology

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.

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 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 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.

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 present application belongs to the technical field of biomedicine, and discloses a chimeric antigen receptor (CAR), an engineered dendritic cell (DC), and a use thereof. The CAR of the present application includes an extracellular domain, a CD8a hinge domain, a CD8a transmembrane domain, and an intracellular domain. The extracellular domain includes a guide sequence and a single-chain antibody sequentially. The intracellular domain includes a Dectin-1 intracellular domain and an intracellular domain of FcR gamma. Chimeric antigen receptor-modified dendritic cells (CAR-DCs) prepared with the CAR of the present application can efficiently recognize a tumor antigen. The combined administration of the CAR-DC and radiotherapy for treating a solid tumor can effectively overcome the immunosuppression of the tumor microenvironment and improve the clinical treatment effect. Therefore, the present application provides an effective immunotherapy strategy for clinical tumor patients, and provides a new idea and method for tumor immunotherapy.

The present invention relates to agents, uses and methods for treating cancer using agents for inhibiting IRF5 expression. Synergistic therapies include agents, uses, and methods for treating cancer using agents for inhibiting IRF5 expression in combination with agents for inhibiting TGF-beta2 expression. In some embodiments, one or more biomarkers, including one or more of IFNGR2, JAK1, and STAT1, and TGF-beta 2 and IRF5, TLR9, FOXP3, CCL22, CREB5, CD8a, CD86, CC14, CD163, ITGAX, and CD11c, can be used to select a subject that can benefit from the method, agent, or use. The agents and compositions may be used in combination with chemotherapy and other standard care therapies.

The invention belongs to the technical field of tumor cell immunotherapy, and particularly relates to an MLLT3 modified CAR-T structure and application thereof. The MLLT3 modified CAR-T provided by the invention has a structure as follows: CD8 [alpha]-TIGIT-CD8 [alpha] TM-41 BB-CD3 [zeta]-P2A-MLLT3, and a structural formula as shown in the specification, the amino acid sequence of the MLLT3 is as shown in SEQ ID NO. 1. The technical defect that in the prior art, when the CAR-T cells are used for preparing the medicine for treating the solid tumor, the T cells are rapidly depleted and die is overcome, the survival period of the CAR-T cells in the solid tumor tissue is effectively prolonged, and a technical foundation is laid for further improving the tumor killing capacity of the CAR-T cells; the method has good application potential and practical value.

The invention relates to a gene composition for HR < + > / HER2 < + > breast cancer immunohistochemical typing and application thereof. The gene composition for HR < + > / HER2 < + > breast cancer immunohistochemical typing comprises the following four genes: a CD8A gene, a KRT5 gene, a GFRA1 gene and a PFKP gene, the HR < + > / HER2 < + > breast cancer immunohistochemical typing result provided by the invention has high consistency with a gold standard RNA sequencing-based molecular typing result, and has guiding significance for clinical treatment of patients, each immunohistochemical subtype has different molecular characteristics, and potential treatment possibility is prompted, so that the HR < + > / HER2 < + > breast cancer immunohistochemical typing method has a wide application prospect. A foundation is provided for clinical application of HR < + > / HER2 < + > breast cancer subtype specific treatment, and the problems that HR < + > / HER2 < + > breast cancer typing operation is complex, sample availability is poor, consumed time and cost are high, and the batch effect is large are solved.

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 invention relates to the field of medical treatment, and discloses a marker combination for predicting the death risk of a sepsis patient during hospitalization and application. The marker combination comprises six T cell subgroups / functional states related to sepsis specificity, and the six T cell subgroups / functional states comprise Treg-FOXP3 + CTLA4 + IL2RA +; the TM is CD8 + Tem-FGFBP2; nKT CCL5 < + > GNLY < + >; the preparation method comprises the following steps of: performing Thelper22-AHR; the method comprises the following steps of: adding a CD8A + Teffector-GZMK; the invention relates to a CD8A + Tem-GZMK cell subset. Six marker genomes of T cell subgroups / functional states obtained through screening have OER specificity at different time points of sepsis patients, the six T cell subgroups / functional states can serve as a set of T cell subgroups related to sepsis specificity, and the T cell subgroups have high application value in sepsis immunotherapy.

The invention discloses a gene marker combination for predicting cancer prognosis, a kit, a system and application, and belongs to the technical field of medical molecular biology. Wherein the gene marker combination is prepared from CD8A, CD79A and CXCL9 (CXCL9). According to the gene marker combination, the kit and the system, cancer prognosis can be accurately evaluated by constructing a risk prediction model, the accuracy is high, and the gene marker combination, the kit and the system have very important clinical application value. In addition, the gene marker combination, the kit and the system can also be used for predicting immunotherapy response, a new detection target is provided for cancer treatment, and precise treatment can be achieved.