36 results about "T-Cell Specificity" patented technology

The invention provides an artificial antigen presenting cell (AAPC) comprising a eukaryotic cell expressing an antigen presenting complex comprising a human leukocyte antigen (HLA) molecule of a single type, at least one exogenous accessory molecule and at least one exogenous T cell-specific epitope. Methods of use for activation of T lymphocytes are also provided.

A family of chimeric antigen receptors (CARs) containing a CD123 specific scFv was developed to target different epitopes on CD123. In some embodiments, such a CD123 chimeric antigen receptor (CD123CAR) gene includes an anti-CD123 scFv region fused in frame to a modified IgG4 hinge region comprising an S228P substitution, an L235E substitution, and optionally an N297Q substitution; a costimulatory signaling domain; and a T cell receptor (TCR) zeta chain signaling domain. When expressed in healthy donor T cells (CD4 / CD8), the CD123CARs redirect T cell specificity and mediated potent effector activity against CD123+ cell lines as well as primary AML patient samples. Further, T cells obtained from patients with active AML can be modified to express CD123CAR genes and are able to lyse autologous AML blasts in vitro. Finally, a single dose of 5.0×106 CAR123 T cells results in significantly delayed leukemic progression in mice. These results suggest that CD123CAR-transduced T cells may be used as an immunotherapy for the treatment of high risk AML.

Described is a method of identifying an immunologically active antigen of a virus that attacks skin, as well as a method of enriching a population of lymphocytes for T lymphocytes that are specific to a virus that attacks skin. Also provided are HSV antigens and epitopes that are useful for the prevention and treatment of HSV infection that have been identified via the methods of the invention. T-cells having specificity for antigens of the invention have demonstrated cytotoxic activity against cells loaded with virally-encoded peptide epitopes, and in many cases, against cells infected with HSV. The identification of immunogenic antigens responsible for T-cell specificity provides improved anti-viral therapeutic and prophylactic strategies. Compositions containing antigens or polynucleotides encoding antigens of the invention provide effectively targeted vaccines for prevention and treatment of HSV infection.

The present invention relates to a novel use of regulatory T cell-specific surface protein Lrig-1, and more specifically to an immunosuppressive agent comprising siRNA which inhibits the expression of surface protein Lrig-1. In addition, the invention relates to a method for screening an immunosuppressive agent which inhibits proteins of Lrig-1 or genes encoding the proteins. As a result, an immunosuppressive agent with low side effects and high specificity can be developed.

A family of chimeric antigen receptors (CARs) containing a CD123 specific scFv was developed to target different epitopes on CD123. In some embodiments, such a CD123 chimeric antigen receptor (CD123CAR) gene includes an anti-CD123 scFv region fused in frame to a modified IgG4 hinge region comprising an S228P substitution, an L235E substitution, and optionally an N297Q substitution; a costimulatory signaling domain; and a T cell receptor (TCR) zeta chain signaling domain. When expressed in healthy donor T cells (CD4 / CD8), the CD123CARs redirect T cell specificity and mediated potent effector activity against CD123+ cell lines as well as primary AML patient samples. Further, T cells obtained from patients with active AML can be modified to express CD123CAR genes and are able to lyse autologous AML blasts in vitro. Finally, a single dose of 5.0 x 106 CAR123 T cells results in significantly delayed leukemic progression in mice. These results suggest that CD123CAR-transduced T cells may be used as an immunotherapy for the treatment of high risk AML.

The invention provides HSV antigens and epitopes that are useful for the prevention and treatment of HSV infection. T-cells having specificity for antigens of the invention have demonstrated cytotoxic activity against cells loaded with virally-encoded peptide epitopes, and in many cases, against cells infected with HSV. The identification of immunogenic antigens responsible for T-cell specificity provides improved anti-viral therapeutic and prophylactic strategies. Compositions containing antigens or polynucleotides encoding antigens of the invention provide effectively targeted vaccines for prevention and treatment of HSV infection.

The invention provides HSV antigens and epitopes that are useful for the prevention and treatment of HSV infection. T-cells having specificity for antigens of the invention have demonstrated cytotoxic activity against cells loaded with virally-encoded peptide epitopes, and in many cases, against cells infected with HSV. The identification of immunogenic antigens responsible for T-cell specificity provides improved anti-viral therapeutic and prophylactic strategies. Compositions containing antigens or polynucleotides encoding antigens of the invention provide effectively targeted vaccines for prevention and treatment of HSV infection.

The invention relates to the technical field of cellular immunity, and discloses a chimeric antigen receptor based on a BMCA nano-antibody sequence and an application thereof, wherein the chimeric antigen receptor includes an extracellular structural domain, a transmembrane structural domain and a primary signal transduction domain. The extracellular structural domain includes an alpaca anti-BCMAantibody or an antigen binding fragment of an alpaca BCMA polypeptide or multiple epitopes. The chimeric antigen receptor is mainly applied in tumor treatment drugs, tumors are blood-related tumor diseases, and the blood-related tumor diseases mainly include various types of leukemia and malignant lymphoma. According to the chimeric antigen receptor based on the BMCA nano-antibody sequence and theapplication thereof, the expression sequence is shorter, and the limited space of a lentiviral vector is saved. The chimeric antigen receptor T cell constructed based on the antibody has better specificity and stronger tumor killing ability.

The invention relates to a bispecific antibody and a preparation method and application thereof. The bispecific antibody contains a structural domain capable of being bound to CD20, a structural domain capable of being bound to CD3 and a heterogeneous dipolymer Fc region, and the structural domain capable of being bound to the CD20 and the structural domain capable of being bound to the CD3 are independently selected from an Fab region, an ScFv region or an sDab region. The bispecific antibody can stably and efficiently target the CD20 and the CD3, and can mediate T-cell specific killing tumorcells.

The invention relates to the technical field of cellular immunity and discloses a construction method and application of a chimeric antigen receptor (CAR) based on a BMCA nano-antibody sequence. The construction method comprises the following steps: step 1: constructing a BMCA single domain antibody library; step 2: screening a BMCA specific nano-antibody sequence; step 3: preparing chimeric antigen receptor T cells. The chimeric antigen receptor is mainly applied to tumor treatment medicines; tumors are tumor diseases related to blood and the tumor diseases related to the blood mainly comprise various leukemia and malignant lymphomas. According to the construction method and application of the chimeric antigen receptor based on the BMCA nano-antibody sequence provided by the invention, the prepared nano-antibody expression sequence is shorter and a limited lentiviral vector space is saved; the chimeric antigen receptor T cells which are constructed based on the antibody have better specificity and a stronger tumor killing capability.

The invention discloses a serum-free medium suitable for culturing gamma delta T cells. The serum-free medium consists of a basal culture medium component I, a gamma delta T cell specific culture component II and water. Experiments show that by adopting the serum-free medium suitable for culturing the gamma delta T cells, the gamma delta T cells obtained is greater in quantity, higher in purity and better in killing effect. The serum-free medium suitable disclosed by the invention has the advantages that 1) the risk of animal components which are used in animal serums in the cell culture with the gamma delta T cells on patients with cell therapy and uncertain impact of uncertain components in the animal serums on the result of the cell culture are avoided; 2) the yield of the gamma delta T cells is greatly improved; and 3) the final density of the gamma delta T cell culture is increased so as to lower the cost of cell culture.

The invention relates to the biotechnical field, and especially relates to a bispecific antibody. The bispecific antibody comprises a first antibody segment and a second antibody segment, the first antibody segment is an antitumor antigen-antibody segment, and the second antibody segment is an anti-human CD3 molecule antibody segment. A bispecific antibody principle is used to construct the Her2 tumor antigen and T cell specific bispecific antibody, and adoptively transferred T cells are used to carry and continuously express the antibody protein in vivo, so the bispecific antibody has an in vivo killing effect, generates enough T effect effects, and optimizes the effect performance efficiency.

The invention provides a method of targeting T-cells to tumor cells using a tumor-associated antigen (TAA) specific antibody and a T-cell specific antibody, wherein the two antibodies can bind to each other through a high affinity avidin / biotin or streptavidin / biotin connection. The invention further provides methods to target activated T-cells to different tumor types by using a T-cell specific antibody that is specific to an activated T-cell surface molecule like CTLA-4.

The invention relates to the technical field of biological engineering, in particular to metabolically modified CAR-T cells and a preparation method and application thereof. According to the method, through biological orthogonal metabolic modification, the CAR-T cells can be effectively targeted and drawn to a tumor site in vivo; in-vivo targeting and drawing leads to combination of specific CAR molecules on the CAR-T cells with tumor antigens on the tumor site, correspondingly the specific activation of the CAR-T cells is stimulated, and a more efficient tumor killing capability is achieved.

The present invention relates to methods for diagnosis of a cellular immune responses against a virus using an inactivated virus. In the method of the invention a cellular immune response against the virus is detected in a subject by incubating PBMCs from the subject with a preparation of inactivated virus and subsequently detecting the expression of at least one T cell specific cytokine in the subject's PBMCs, preferably by flow cytometry. Advantageously in the method, inactivated virus is used for incubation with PBMCs from the subject so as to make feasible that the method is performed in laboratories without BSL-3 classification. Preferably the method is a method for detecting a CD4+ and / or CD8+ T cell response against an influenza virus by detecting expression of one or more of CD107, IFN-γ, IL-2, IL-10 and TNF-α, using formalin inactivated influenza virus. The invention further pertains to kits comprising components that are useful for detecting a cellular immune responses in a subject against a virus.

The invention discloses combined application of an oncolytic virus and CAR-T, mainly directing at treatment of solid tumor. As a carrier of the oncolytic virus for treating the solid tumor, the CAR-Tcarries the oncolytic virus to a solid tumor location, so that the defect of undesirable killing effect on the solid tumor of the CAR-T is overcome, and the oncolytic virus is not separately exposed to a humoral immunity environment. The oncolytic virus is specifically carried and delivered to the solid tumor location according to a solid tumor target of the CAR-T, so that the cancer cell lysis ability of the oncolytic virus and the specific target cell killing ability of a CAR-T cell are brought into full play.

The present invention provides novel methods for immunotherapy. The invention provides immune cells and methods to generate them, with the capacity to at least in part reduce an immune response in a host. In one aspect, the invention provides a method for generating a dendritic cell with the capacity to tolerize a T-cell for antigen the T-cell was specific for including culturing peripheral blood monocytes from an individual to differentiate into dendritic cells, activating the dendritic cells in the presence of a glucocorticoid hormone and loading the activated dendritic cell with the antigen the T-cell was specific for.

The present invention relates to a humanized scFv delivery vehicle targeted to be human T-cell specific, and provides: a humanized scFv which comprises a heavy-chain variable region (VH) consisting of a polypeptide comprising an amino acid sequence given by sequence number 32 and comprises a light-chain variable region (VL) consisting of a polypeptide comprising an amino acid sequence given by sequence number 34; and a T-cell-specific drug or marker delivery vehicle comprising the humanized scFv. The humanized scFv of the present invention has minimalised antigenicity and has an effect which does not give rise to an immune reaction even when used in the human body, and thus can advantageously be used as a delivery vehicle for specifically delivering a target substance such as a siRNA gene or an immune reaction regulating protein to T-cells.

The present invention relates to chimeric antibody receptors with anti-cotinine antibodies linked, and use thereof. A T cell presenting the chimeric antibody receptor on the surface secretes interferon gamma specifically for a target molecule of a cotinine-conjugated binding molecule that is added together therewith and induces cell death of the cell expressing the target molecule by the T cell. On the contrary, by administering a cytotoxic agent conjugated with cotinine, cell death of the chimeric antigen receptor T cell is induced. Therefore, if necessary, a cytotoxic agent conjugated with cotinine can be administered to remove the chimeric antigen receptor T cells that have been already administered, thereby suppressing immune side effects due to hyperactivity of T cells. Thus, the chimeric antigen receptor to which the anti-cotinine antibody is linked can be effectively and safely used for the treatment of cancer.

The present invention provides a method for altering a T cell mediated pathology in a patient. This method comprises administering a composition comprising at least one and / or two chimeric proteins. Each chimeric protein comprises at least a portion of either the Valpha or Vbeta region of a TCR from particular T cells from a patient having a T cell mediated pathology, and an immunoglobulin constant region. The genes encoding Valpha and / or Vbeta regions and the genes encoding immunoglobulin constant regions are isolated and inserted into an expression vector. The chimeric proteins are produced by introducing the expression vectors into insect cell lines. The chimeric proteins are purified using antibody affinity columns, and then chemically conjugated to an immunogenic carrier, keyhole-limpet hemocyanin (KLH). Since the conjugates comprises chimeric proteins made specifically from particular T cells from a patient having T cell mediated pathology, when it is administered to such a patient, with or without a cytokine, such as granulocyte-macrophage-CSF, or a chemokine, it can induce immune responses to alter such a T cell mediated pathology.

The culture method to differentiate embryonic stem cell into T cell comprises: preparing embryo body; transferring the body into differentiated culture medium; digesting the body into single cell by pancreatin; labeling the opposite antibody of T cell special surface cell; detecting T cell quantity with a FCM; and obtaining the need T cell. It also provides the opposite culture medium. This invention overcomes the defect in prior art, induces T lymphocyte from embryonic stem cell directly, and provides a simple and effective external model for research and a safe source for clinical application of T cell.

The present invention relates to a humanized scFv delivery vehicle targeted to be human T-cell specific, and provides: a humanized scFv which comprises a heavy-chain variable region (VH) consisting of a polypeptide comprising an amino acid sequence given by sequence number 32 and comprises a light-chain variable region (VL) consisting of a polypeptide comprising an amino acid sequence given by sequence number 34; and a T-cell-specific drug or marker delivery vehicle comprising the humanized scFv. The humanized scFv of the present invention has minimalised antigenicity and has an effect which does not give rise to an immune reaction even when used in the human body, and thus can advantageously be used as a delivery vehicle for specifically delivering a target substance such as a siRNA gene or an immune reaction regulating protein to T-cells.

The invention discloses a human-derived CD-19 chimeric antigen receptor T lymphocyte vector which is characterized by comprising a plasmid vector for coding single-chain variable region genes of CD19monoclonal antibodies, nucleosomal histone monoclonal antibodies and FNEDB monoclonal antibodies. The vector is a lentiviral vector. The invention further discloses application of the human-derived CD-19 chimeric antigen receptor T lymphocyte vector in preparation of CATR cells. The vector is used for transduction of T lymphocytes, natural killer cells and mononuclear cells, and is applied to treating tumors, preferably treating reoccurrence in malignant lymphoma drugs as well as neoplastic hematologic disorders and lymphomas which are refractory and unsuccessful in bone marrow transplantationmatching. The human-derived CD-19 chimeric antigen receptor T lymphocyte vector disclosed by the invention has the beneficial effects that the vector constructed in the invention can achieve the effects of enhancing the targeted CD19 antigen transgenic T lymphocyte specificity, overcoming the tumor microenvironment inhibited immune cellular function and controlling cytokine storm in clinic treatment.

The invention relates to a method of detecting specific killing effects of chicken spleen CD8<+>T cells based on flow cytometry. The method comprises a first step of bacterial culture in which the bacteria are salmonella pullorum S06004 and S06004deltaspiC, a second step of chick immunization and sampling, a third step of target cell-macrophage preparation, a fourth step of effector cell-chicken spleen CD8<+>T cell preparation which comprises a substep of preparation of a chicken spleen lymphocyte suspension and a substep of magnetic bead sorting of a chicken spleen CD8<+>T cell and a fifth step of specifically killing macrophage by CTL. Compared with the prior art, the method disclosed in the invention has the following beneficial effects that the macrophage (target cell) obtained by adherence has high purity, the sorting effects for chicken spleen CD8<+>T cells are obvious, and the separation time is short; with the salmonella host cell- macrophages as the target cell, the salmonellaremoving ability by the host can be reflected more accurately; and the flow cytometry is used for chicken spleen CD8<+>T cell specific killing effects and can detect the CTL effects of the chicken spleen CD8<+>T cell in a single cell level.

This invention is related to a peptides mixture. Without the need to consider the patients' genetic background, it can interfere with MHC-pathogenic peptide-TCR formation, which includes the interference with pathogen peptide binding with MHC and pMHC binding with specific TCR, suppression of the immune synapse formation when the specific T cell immune response occurs, reduction of the number and density of the MHC-specific immune response mediated pathogenic peptide-TCR in the immune synapse, and suppression of the highly activated signal transduction in the immune synapse. Hence it can negatively regulate the T cell specific immune response, reduce the specific immune cell activation, proliferation and effect, and make the radical T cell specific immune response more stable and last longer. It can be used to treat diseases with excessive T cell-specific immune reaction, such as severe flu, SARS, hand-foot-and-mouth disease, viral pneumonia, bacterial infections, severe autoimmune disease and etc.

The invention provides epitopes of HSV and VZV that are cross-reactive and are useful for the prevention and treatment of alphaherpesvirus infection. T-cells having specificity for antigens of the invention have demonstrated cytotoxic activity against cells loaded with virally-encoded peptide epitopes, and in many cases, against whole virus. The identification of immunogenic antigens responsible for T-cell specificity provides improved anti-viral therapeutic and prophylactic strategies. Compositions containing epitopes or polynucleotides encoding epitopes of the invention provide effectively targeted vaccines for prevention and treatment of alphaherpesvirus infection.

The invention relates to a polypeptide mixture for interfering the formation of MHC (Major Histocompability Complex)-pathogenic peptide-TCR (Cell Antigen Receptor) regardless of the genetic background of patients. The formation of MHC-pathogenic peptide-TCR is interfered by the following steps of: interfering the combination of pathogenic peptide and MHC and the combination of pMHC and the specific TCR; inhibiting the formation of immunological synapse generated by a specific T-cell immunoreaction; inhibiting the number and the density of MHC-specific immunoreaction mediated pathogenic peptide-TCR in the immunological synapse; and inhibiting the transmission of an intense activation signal in the immunological synapse and negatively adjusting the ongoing intense specific immunoreaction mediated by the T-cell; weakening the activation, multiplication and effect capabilities of specific immunocyte so that extreme T-cell specific immunoreaction becomes milder and durable. The invention is used for treating diseases accompanied by the extreme T-cell specific immunoreaction, such as serious flu, SARS (Severe Acute Respiratory Syndrome), hand-foot-and-mouth diseases, viral pneumonia, bacterial infection, serious self immune diseases, and the like.

The invention provides HSV antigens that are useful for the prevention and treatment of HSV infection, including epitopes confirmed to be recognized by T-cells derived from herpetic lesions. T-cells having specificity for antigens of the invention have demonstrated cytotoxic activity against cells loaded with virally-encoded peptide epitopes, and in many cases, against cells infected with HSV. The identification of immunogenic antigens responsible for T-cell specificity provides improved anti-viral therapeutic and prophylactic strategies. Compositions containing antigens or polynucleotides encoding antigens of the invention provide effectively targeted vaccines for prevention and treatment of HSV infection.

The present invention relates to methods for diagnosis of a cellular immune responses against a virus using an inactivated virus. In the method of the invention a cellular immune response against the virus is detected in a subject by incubating PBMCs from the subject with a preparation of inactivated virus and subsequently detecting the expression of at least one T cell specific cytokine in the subject's PBMCs, preferably by flow cytometry. Advantageously in the method, inactivated virus is used for incubation with PBMCs from the subject so as to make feasible that the method is performed in laboratories without BSL-3 classification. Preferably the method is a method for detecting a CD4+ and / or CD8+ T cell response against an influenza virus by detecting expression of one or more of CD107, IFN-γ, IL-2, IL-10 and TNF-α, using formalin inactivated influenza virus. The invention further pertains to kits comprising components that are useful for detecting a cellular immune responses in a subject against a virus.