78 results about "Anti-CD3 Antibody" patented technology

The present invention provides antibodies that bind to CD3 and methods of using the same. According to certain embodiments, the antibodies of the invention bind human CD3 with high affinity and induce human T cell proliferation. The invention includes antibodies that bind CD3 and induce T cell-mediated killing of tumor cells. According to certain embodiments, the present invention provides bispecific antigen-binding molecules comprising a first antigen-binding domain that specifically binds human CD3, and a second antigen-binding molecule that specifically binds human CD20. In certain embodiments, the bispecific antigen-binding molecules of the present invention are capable of inhibiting the growth of B-cell tumors expressing CD20. The antibodies and bispecific antigen-binding molecules of the invention are useful for the treatment of diseases and disorders in which an upregulated or induced targeted immune response is desired and / or therapeutically beneficial. For example, the antibodies of the invention are useful for the treatment of various cancers as well as other CD20-related diseases and disorders.

The present invention provides methods of treating, preventing or ameliorating the symptoms of T cell-mediated immunological diseases, particularly autoimmune diseases, through the use of anti-CD3 antibodies. In particular, the methods of the invention provide for administration of antibodies that specifically bind the epsilon subunit within the human CD3 complex. Such antibodies modulate the T cell receptor / alloantigen interaction and, thus, regulate the T cell mediated cytotoxicity associated with autoimmune disorders. Additionally, the invention provides for modification of the anti-CD3 antibodies such that they exhibit reduced or eliminated effector function and T cell activation as compared to non-modified anti-CD3 antibodies.

The present invention provides methods for treating, reducing the severity, or inhibiting the growth of cancer (e.g., a B-cell cancer such as Hodgkin's lymphoma or acute lymphoblastic leukemia). The methods of the present invention comprise administering to a subject in need thereof a therapeutically effective amount of an antibody or antigen-binding fragment thereof that specifically binds to programmed death 1 (PD-1) receptor in combination with a therapeutically effective amount of a bispecific antibody that specifically binds to CD20 and CD3.

Disclosed are immunopotentiating agents, and vaccines thereof, which enhance and / or otherwise modify immune responses, and method for their preparation and use in vivo. Immunopotentiating agents can be single agents that act directly, adjuvants added concurrently with the agents, or heteroconjugates wherein the immunopotentiating agent is chemically coupled to the compound against which an immune response is desired. Examples of immunopotentiating agents include monoclonal antibodies, such as anti-CD3, anti-CD2) and anti-CD5 antibodies, and proteins derived from microorganisms (e.g., enterotoxins) which activate T cells. The compounds against which an immune response can be generated, which may be the second component in a heteroconjugate, include compound from abnormal or diseased tissues such as tumors, or infectious agents, such as viruses, bacteria, fungi, protozoal or metozoal parasites, and can be obtained by natural or recombinant means. Methods of using the invention to prepare monoclonal antibodies are particularly disclosed.

The present invention provides methods for treating, reducing the severity, or inhibiting the growth of acute lymphoblastic leukemia. The methods of the present invention comprise administering to a subject in need thereof a therapeutically effective amount of a bispecific antibody that specifically binds to CD20 and CD3.

The invention is related to a recombinant single-chain tri-specific antibody made from anti-Tumor Associated Antigen (TAA) antibody, FC interlinker, anti-CD3 antibody, HSA interlinker and anti-CD28 antibody in turn. Particularly, the invention relates to an anti-CEA, anti-CD3, anti-CD28 recombinant single-chain tri-specific antibody, CEA-scTsAb, which was constructed with three tandem antibody fragments (anti-CEA scFv, anti-CD3 scFv and anti-CD28 single-domain antibody) linked by two interlinkers (FC interlinker, HSA interlinker), and could be appended by C myc tag or histidine tag ((His)6-tag) at the C terminal. It also concerns a method for construction, expression and purification of the antibody. It also offers the encoded DNA sequence of the antibody, expression vectors and host cells for the vectors.

The invention provides methods for treating autoimmunity and for reestablishing tolerance. The methods involve the coadministration of anti-CD3 antibodies and self-antigens. The coadministration has the potential to provide a synergistic effect of protecting or reducing autoaggressive immune processes and / or of reestablishing tolerance towards self-antigens. An underlying rationale behind the methods is that the administration of self-antigens together with anti-CD3 antibodies can alter the response to those self-antigens and prevent progression of autoimmunity. By rechallenging with the autoantigens and stimulating the non-pathogenic response, the blockade of the autoimmune process can be maintained. Preclinical evidence provided herein shows that the combination of anti-CD3 and autoantigen is synergistic in reversing autoimmune diabetes, and therefore, suggests that combination therapy of anti-CD3 and self-antigen may provide synergistic protection in reversing other autoimmune disorders.

The invention discloses a method for simultaneous and efficient amplification of CD<3+>CD<56+>CIK cells and CD<3->CD<56+>NK cells. The method comprises the steps as follows: the concentration of separated PBMC (peripheral blood mononuclear cells) is adjusted by a serum-free medium containing autologous plasma, an Anti-CD16 antibody, IL-2 and IL-15 are added, and then the mixture is transferred into a T175 culture flask for culture; an Anti-CD3 antibody and an Anti-CD137 antibody are added; a serum-free medium containing the autologous plasma, IL-2 and IL-15 is supplemented every two days according to the cell growth condition; the cell concentration is controlled to be about 1.5*10<6> / ml; and after culture is performed for 14-21 days, large quantities of high-purity CD<3+>CD<56+>CIK cells and CD<3->CD<56+>NK cells can be obtained simultaneously, and the total cell quantity can reach an effective value of the cell quantity required for adoptive cellular immunotherapy clinically for tumor. The method for simultaneous and efficient amplification of the CD<3+>CD<56+>CIK cells and the CD<3->CD<56+>NK cells is simple, convenient, effective and high in cell killing activity.

In certain embodiments methods are provided for the therapeutic or prophylactic amelioration of one or more symptoms or disorders associated with metabolic syndrome. In various embodiments the methods involve administering to a subject in need thereof, a GABA receptor agonist, in an amount sufficient to ameliorate said one or more symptoms. In certain embodiments methods are provided for the prophylaxis or treatment of type I diabetes and related pathologies that involve the use of GABA or GABA agonists in combination with certain other compounds (e.g., one more antigens (e.g., GAD) that have a therapeutic effect in type I diabetes and / or an anti-CD3 antibody, an anti-CD20 antibody, exendin-4, and / or or a pro-insulin therapeutic).

The invention discloses culturing, freezing and recovering methods of an activated lymphocyte with CD3+CD8+as major, which can solve problems that a patient needs carrying out blood sampling for many times caused by continuously utilizing the activated lymphocyte with CD3+CD8+as major. The method comprises the following steps of: (1) contacting the extracted lymphocyte of the peripheral blood with IL-2, IL-15, an anti-CD3 antibody and an anti-CD28 antibody, so as to amplify the activated lymphocyte with CD3+CD8+as major; (2) freezing and storing the activated lymphocyte; and (3) recovering the activated lymphocyte. The activated lymphocyte cultured via the method disclosed by the invention has clear components, and comprises few CD4+CD25+Treg cells and more CD8+T lymphocyte; feedback time and frequency of the activated lymphocyte can be adjusted according to other treatments for a patient, such as a radiotherapy or a chemotherapy, so that diseases, such as tumor, infectious diseases and immunodeficiency can be treated well.

Non-toxic anti-CD3 antibody is useful for the treatment, prevention, and reversal of human autoimmune disease. Anti-CD3 antibody is generated by immunizing xenogenic mice capable of developing fully human antibodies. Because the inventive antibodies are not derived from other species, they do not the invoke the immune responses typically associated with humanized or grafted antibodies.

The invention provides methods for treating autoimmunity, for reestablishing tolerance, and for generally dampening or suppressing the activation state of the immune system. The methods involve the induction or activation of a particular regulatory T cell population, characterized by its expression of CD8, CD25 and Foxp3.

The disclosure relates to methods of manufacturing T cells for adoptive immunotherapy. The disclosure further provides for methods of genetically transducing T cells, methods of using T cells, and T cell populations thereof. In an aspect, the disclosure provides for methods of thawing frozen peripheral blood mononuclear cells (PBMC), resting the thawed PBMC, activating the T cell in the cultured PBMC with an anti-CD3 antibody and an anti-CD28 antibody immobilized on a solid phase, transducing the activated T cell with a viral vector, expanding the transduced T cell, and obtaining expanded T cells.

The present invention provides methods of treating, preventing or ameliorating the symptoms of T cell-mediated immunological diseases, particularly autoimmune diseases, through the use of anti-CD3 antibodies. In particular, the methods of the invention provide for administration of antibodies that specifically bind the epsilon subunit within the human CD3 complex. Such antibodies modulate the T cell receptor / alloantigen interaction and, thus, regulate the T cell mediated cytotoxicity associated with autoimmune disorders. Additionally, the invention provides for modification of the anti-CD3 antibodies such that they exhibit reduced or eliminated effector function and T cell activation as compared to non-modified anti-CD3 antibodies.

The invention discloses a composition capable of stimulating expansion of T cells. Active factors of the composition comprise an Anti-CD3 antibody, an Anti-CD28 antibody, IL-2, IL-7 and IL-21. Through an HIV-1 specificity polypeptide combination and a multiple cell factor combination, in-vitro expansion of the antigen-specific memory T cells (TSCM and TCM) of an HIV-1 infected person can be effectively and continuously stimulated, and meanwhile the proportion of the expanded CD8<+> memory T cells, especially the CD8<+> TSCM is increased. The half-life period of adoptive immunotherapy reinjection cells can be prolonged, therefore, the immune surveillance achieving ageing of the adoptive immunotherapy reinjection cells is prolonged, and the potential of controlling HIV-1 latent infection for a long term is achieved. According to the method, the advantages that operation is simple, and materials are easy to obtain are achieved, and good technical support is supplied to wide development of anti-infection adoptive immunotherapy.

Antibodies or functional antibody fragments that recognize or interfere with the production of a component of the CD3 antigen complex are de-immunized.

The present invention relates to an improved growth method for natural killer cells (NK cells). More specifically, the present invention relates to a growth method for natural killer cells, which comprises a step of culturing natural killer cells in a medium containing anti-CD3 antibodies and interleukin proteins in the presence of peripheral blood leukocytes. The present invention provides an innovative growth method for natural killer cells, which can obtain a large amount of natural killer cells by remarkably increasing the growth rate compared with conventional growth methods for natural killer cells.

The invention discloses a method for simultaneously inducing and amplifying V alpha<24+>iNKT cells and CD<3->CD<56+>NK cells. The method comprises the steps as follows: PBMC (peripheral blood mononuclear cells) are separated from peripheral blood, the concentration of the PBMC is adjusted to 2*10<6> / ml by a serum-free medium containing autologous plasma; an Anti-CD<16> antibody, -GalCer, IL-2, IL-18 and IL-21 are added, and then the mixture is transferred into a culture flask for culture; an Anti-CD3 antibody is added in a cell suspension in 24 hours; a serum-free medium containing IL-2, IL-18 and IL-21 is supplemented every two days according to the cell growth condition; the cell concentration is controlled to be 1.5*10<6> / ml; and after continuous culture is performed for 14-21 days, large quantities of high-purity V alpha<24+>iNKT cells and CD<3->CD<56+>NK cells can be obtained simultaneously, and the total cell quantity can reach an effective value of the cell quantity required for adoptive cellular immunotherapy clinically for tumor. The method for simultaneous and efficient amplification of the V alpha<24+>iNKT cells and the CD<3->CD<56+>NK cells is simple, convenient and effective.

The present invention provides a method of treating autoimmune diseases. In particular, it provides a method for the treatment of ulcerative colitis or Crohn's disease comprising administering to a subject a therapeutically effective amount of a pharmaceutical formulation comprising an antibody, wherein said antibody binds to CD3.

Autoimmune disease is treated by the delivery of a suppressive agent to the site of disease. Delivery is accomplished by introducing an expression vector encoding the suppressive agent into cells targeted for such sites, and administering the genetically modified cells to the patient. Suppressive agents of particular interest include IL-4; and anti-CD3 antibodies, particularly single chain anti-CD3 antibodies. Cells of interest for delivery include T cells and T cell hybridomas, where the T cell antigen receptor recognizes epitopes associated with the autoimmune disease. Alternatively, dendritic cells are used as delivery vectors.

The present invention provides an anti-ovarian cancer bispecific antibody. Said antibody includes two polypeptide domains connected by a polypeptide linker, one is anti-ovarian cancer antibody, or its Fab fragment, single complementarity determining region (CDR) antibody or single chain Fv (scFv) and the other is anti-CD3 antibody, or its Fab fragment, single CDR antibody or scFv. The present invention also provides DNA sequences encoding said antibody, an expression vector containing said DNA sequence, and a host cell containing said expression vector.

The invention belongs to the field of immunological technique and discloses a T lymphocyte immunophenotyping method and a kit. The T lymphocyte immunophenotyping method provided by the invention comprises the following steps: taking different fluorescently-labeled antibodies and mixing the antibodies with a sample to be tested, carrying out incubation, carrying out flow cytometry detection to obtain test data, and analyzing the test data. The antibodies contain an anti-TCR alpha beta antibody, an anti-TCR gamma Delta antibody, an anti-CD3 antibody, an anti-CD4 antibody, an anti-CD8 antibody, an anti-CD27 antibody and an anti-CD45RA antibody. By the above method, more comprehensive fine T lymphocyte immunophenotyping is realized. Few samples to be tested are required. The method is simple to operate. Required time is short. And the method has high accuracy and can widely be applied in lymphocyte subpopulation immunophenotyping.

Provided is a medium composition for culturing self- activated lymphocytes applicable to the treatment of malignant tumors, to which anti-CD3, anti-CD16 and anti-CD56 antibodies are added along with interleukin2 (IL-2) to evenly activate natural killer (NK) cells, T cells and natural killer T (NKT) cells, and thus the medium composition can be used to culture im- munocytes that can effectively treat various kinds of malignant tumors. The medium composition includes a cell culture medium and additives added to the cell culture medium, wherein the additives include interleukin2 (IL-2), anti-CD3 antibodies, anti-CD16 antibodies, and anti-CD56 antibodies.

The invention belongs to the field of biotechnology development and application and discloses a preparation method of HLA-A0201 restriction AFP antigen specific CTL. The method is characterized in that peripheral blood mononuclear cells are collected through hemapheresis, and CD8+T lymphocytes are enriched and purified; mature dendritic cells loaded with HLA-A0201 restriction AFP antigen polypeptides are used to stimulate the CD8+T lymphocytes, and rhIL-2 and rhIL-7 are combined to promote the growth of the CD8+T lymphocytes; a Tetramer marking method and a fluorescence-activated cell sorting method are used to purify the target CTL; a solid-phase-coated anti-CD3 antibody and IL-2 are used to stimulate the growth of the target CTL; autologous PBMC irradiated by gamma rays is added to enhance the activation of the target CTL; rhIL-15 is added for culture amplification, and collection and identification are performed. The target CTL prepared by the method is high in purity, high in proliferation ability, high in killing activity, high in CTL-CM proportion, and applicable to immunological treatment of tumors and the like.

Disclosed is a method for preparing activated lymphocytes, which comprises isolating lymphocytes from peripheral blood and proliferating and activating the isolated lymphocytes in vitro. According to the disclosed method, highly effective toxic cells can be prepared in large amounts by culturing human peripheral lymphocytes in the presence of an anti-CD3 antibody, IFN-γ and IL-2. The activated lymphocytes proliferated according to the disclosed preparation method comprise both CD3-CD56+ (natural killer cell marker) cells that are the main components of LAK cells, and CD3+CD56+ cells that are the main components of CIK cells, and can be cultured in large amounts. Thus, the lymphocyte cells can show a significantly higher anticancer effect compared to when the LAK cells and the CIK cells are used alone.

Disclosed is a medium composition for culturing self-activated lymphocytes, which contains anti-CD3 antibody and anti-CD16 antibody in addition to interleukin 2 (IL-2), interleukin 12 (IL-12) and interleukin 18 (IL-18) in a medium, and thus can efficiently proliferate and activate NK cells, T cells and NKT cells and, at the same time, can significantly increase the ratio of NK cells in lymphocytes so as to provide immunocytes having excellent effects on the treatment of various kinds of malignant tumors, and a method for culturing self-activated lymphocytes using the medium composition.

It is intended to provide a method for producing an NK cell-enriched blood preparation, which is low invasive and is capable of conveniently and rapidly growing NK cells, etc. in blood collected from an organism. The NK cells in blood are stimulated with NK cell growth-stimulating factors comprising an anti-CD16 antibody, OK432, an anti-CD3 antibody, and a cytokine. Then, the blood is cultured at a physiological cell temperature to produce an NK cell-enriched blood preparation.

Disclosed is a medium composition for culturing self-activated lymphocytes, which contains anti-CD3 antibody and anti-CD16 antibody in addition to interleukin 2 (IL-2), interleukin 12 (IL-12) and interleukin 18 (IL-18) in a medium, and thus can efficiently proliferate and activate NK cells, T cells and NKT cells and, at the same time, can significantly increase the ratio of NK cells in lymphocytes so as to provide immunocytes having excellent effects on the treatment of various kinds of malignant tumors, and a method for culturing self-activated lymphocytes using the medium composition.