43 results about "CD1D" patented technology

The invention is directed to a compound comprising one or more CD1d complexes in association with an antibody specific for a cell surface marker. The CD1d complexes comprise a CD1d, a β2-microglobulin molecule, and may further comprise an antigen bound to the CD1d binding groove. The invention is further directed to methods of inhibiting or stimulating an immune response with the CD1d-antibody compounds, in particular anti-tumor and autoimmunity responses.

The invention is directed to methods of modulating an immune response in an animal, comprising administering a composition comprising one or more soluble CD1d complexes, in particular non-specific soluble CD1d complexes. Soluble CD1d complexes comprise a soluble CD1d polypeptide, a β2-microglobulin polypeptide, and a ceramide-like glycolipid antigen bound to the CD1d antigen binding groove, and in certain embodiments, an immunogen. The administration of compositions of the present invention affects the activity of CD1d-restricted NKT cells, and in particular, allows for multiple administrations without causing CD1d-restricted NKT cell anergy.

α-Galactosylceramides and glycosylceramides (“ceramide-like glycolipids”) that modulate NK T cells. The ceramide-like glycolipids vary in the cytokines induced in NK T cells and vary in the antigen-presenting cells that are capable of efficiently presenting the compounds to NK T cells. Pharmaceutical compositions of the ceramide-like glycolipids are provided, as are pharmaceutical compositions of the ceramide-like glycolipids combined with dendritic cells. Methods utilizing the ceramide-like glycolipids in vaccines, to activate NK T cells, to stimulate the immune system, and to treat mammals are also provided. The invention also provides methods of evaluating a compound for its ability to activate an NK T cell in the presence of a cell expressing a CD1d protein.

α-Galactosylceramides and glycosylceramides (“ceramide-like glycolipids”) that modulate NK T cells. The ceramide-like glycolipids vary in the cytokines induced in NK T cells and vary in the antigen-presenting cells that are capable of efficiently presenting the compounds to NK T cells. Pharmaceutical compositions of the ceramide-like glycolipids are provided, as are pharmaceutical compositions of the ceramide-like glycolipids combined with dendritic cells. Methods utilizing the ceramide-like glycolipids in vaccines, to activate NK T cells, to stimulate the immune system, and to treat mammals are also provided. The invention also provides methods of evaluating a compound for its ability to activate an NK T cell in the presence of a cell expressing a CD1d protein.

The present invention provides a method of selectively augmenting an immunosuppressive function in various functions of NKT cells, and a method of efficiently inducing an antigen specific immunosuppression in vivo, as well as a pharmaceutical obtained by applying the same.

More particularly, the present invention provides a pharmaceutical (e.g., a preventive or therapeutic agent for immune diseases such as allergic disease and autoimmune disease) containing a CD1d ligand and a target antigen (e.g., allergen, autoantigen). Preferably, the pharmaceutical contains a drug delivery vehicle including the CD1d ligand and the target antigen and having a lumen.

The present invention is directed to a method of inhibiting CD1d activation by administering a composition containing a moiety that blocks CD1d activation. Compositions of the invention are useful for the attenuation of CD1d-restricted immune responses, including treatment of skin disorders due to hyperactive immune responses (e.g., contact hypersensitivity), for systemic administration to attenuate ongoing immune responses, and to provide hypoallergenic cosmetic products including pharmaceutical, cosmetic, and skin care compositions. Preferably, these compositions are in a form intended for topical administration.

The invention provides compounds and methods for the ex vivo or in vivo expansion of NK T cells, CD1d-reactive T cells, and JαQ⁺ T cells, and the modulation of their activities. These compounds and methods have diagnostic and therapeutic applications.

The present invention relates to methods of obtaining antigen-specific regulatory cells in vitro or in vivo. The regulatory cells are obtainable by inducing apoptosis of antigen-presenting cells by NKT cells. In particular, NKT cells are elicited, in vitro or in vivo, by exposure to CD1d-restricted NKT cell peptide epitopes either in natural configuration or modified as to contain a thioreductase motif within flanking residues. The present invention discloses methods to elicit immature antigen-presenting cells loaded with apoptotic cells or with apoptotic bodies for suppressing or preventing diseases such as autoimmune diseases, graft rejection and allergic diseases, and medicaments related thereto. Further disclosed are the use of antigen-specific regulatory cells for suppressing or preventing diseases such as autoimmune diseases, graft rejection and allergic diseases, and medicaments related thereto. Further disclosed are populations of antigen-specific regulatory cells obtained by this method.

The present invention is directed to a method of inhibiting allergen-induced airway CD1d activation by administering a composition containing a moiety that blocks CD1d activation. Methods of the invention are useful for treatment and prevention of air-way hyperactivity caused by an allergen, and results in the attenuation of CD1d-restricted immune responses, including treatment of hay fever and asthma are due to air-way hyperactivity, and for systemic administration to attenuate ongoing immune responses. Preferably, these compositions are in a form intended for administration via nasal passages or directly inhaled to the air-ways.

The present invention provides a means to be used for a new immunotherapy of cancer or infection utilizing activation of dendritic cell (DC) by innate immunity, namely, a method of preparing a cell co-expressing a target antigen and CD1d and having an ability to activate immunity against the target antigen, comprising the following steps (a) and (b):

(a) a step of transfecting an mRNA encoding the target antigen into a CD1d-expressing cell to give a cell co-expressing the target antigen and CD1d; and (b) a step of treating the cell obtained in step (a) with a CD1d ligand in a culture medium.

The invention relates to a manipulated professional antigen presenting cell (APC) having increased expression of a CD1 type II molecule, preferably at least a CD1d molecule, relative to a control non manipulated cell. The invention further relates to the use of PPARg modulators in the preparation of a pharmaceutical composition or kit for the treatment of a disease treatable by activation of CD1d restricted T-cells, e.g. in autoimmune diseases, allergies, post-transplant conditions or infectious diseases, or in the treatment of a neoplastic disease, e.g. skin cancer, hematological tumors, colorectal carcinoma, and therapeutic compositions and kits therefor. Furthermore, the invention relates to methods of manipulating professional APCs and kits therefor.

The present invention provides a superior method of functional analysis of NKT cells, which enables function analysis of low frequency NKT cells, is independent of the function of autologous APCs, and can avoid an influence of secondary factors and the like. More specifically, the present invention provides a method of functional analysis of human NKT cells including (a) cocultivating a mononuclear cell derived from human peripheral blood with a CD1d-expressing antigen presenting cell derived from a heterologous animal, and (b) evaluating the functionality of NKT cells with the number of NKT cells and/or a substance specific to functional NKT cells as an index; a reagent for analysis of human NKT cells containing a CD1d-expressing antigen presenting cell derived from a heterologous animal; a kit containing (a) a CD1d-expressing antigen presenting cell derived from a heterologous animal, and (b) at least one reagent selected from the group consisting of a reagent for selection of human mononuclear cell, a reagent for measurement of the number of human NKT cells and a reagent for measurement of a substance specific to human functional NKT cells; and the like.

The manipulation of human dendritic cells (DCs) to induce potent anti-tumor immunity remains an essential subject of study. Here we report that the overexpression of CD1d in human DCs can enhance the priming of naïve CD8+ T cells against tumor antigen. We showed that CD1d can be overexpressed in the human DCs using baculoviral vector carrying the CD1d gene. This CD1d-overexpression is functional as demonstrated by the increased expansion of invariant natural killer T (iNKT) cells while using these modified DCs to present α-galactosylceramide (α-GC). Pulsed with tumor antigenic peptide, these CD1d-overexpressing human DCs showed enhanced capability to prime naïve CD8+ T cells. CD1d-overexpressing human DCs also induced a pro-inflammatory cytokine profile that may favor the priming. Moreover, this CD1d-overexpression strategy can be extrapolated to monocyte-derived human DCs. Therefore, our study suggest that overexpression of CD1d in human DCs may provide a novel strategy to enhance DC immunogenicity and the possible translation into human cancer immunotherapy.

The invention discloses a method for constructing an HSAT H-T-S human-mouse chimera model and the application thereof. Firstly, a female Nod-SCID mouse in 6-8 weeks is selected; whole body exposure is carried out on the SCID mouse by radiation; secondly, human embryo thymic cells are taken; the cells come from the thymus of the embryo of a person who is voluntary to terminate the pregnancy, and the pregnant week is less than 24 weeks; the quantity of the cells is 1*10<7>, wherein, the quantity proportion of the thymic cells, as well as thymic epithelia and other stroma cells is 1:1, and the specificity of alpha-GalCer-CD1d tetramer is used for eliminating young and mature NKT cells; thirdly, the obtained embryo thymic cells are injected to the thymus of the SCID mouse subcutaneously to carry out dermatoplasty and obtain an HSAT H-T-S human-mouse chimera model. In the method, the human embryo thymic cells are implanted to the thymus of the mouse with severe combined immunodeficiency, and the full skin of human embryo trunk is grafted to the chest cavity of the SCID mouse, thereby reproducing the immune tolerance and rejection reaction of the dermatoplasty reaction in human body. The invention has good repeatability, obvious effect, simple method and good application prospect.

An isolated human NKT cell or a plurality of cells thereof, having reduced or no detectable expression of endogenous beta-2-microglobulin (B2M); endogenous MHC class II-associated invariant chain (Ii); or both. Methods to generate the cell or cells, and methods of treatment using the cell or cells are also provided.

The invention relates to compounds, in particular polypeptides that specifically bind to the non-classical MHC protein CD1d and modulate CD1d-mediated biological functions. The invention in particularrelates to such compounds and polypeptides comprising or consisting of at least one single domain antibody, and wherein at least one single domain antibody specifically binds to CD1d. Also provided is for methods and use employing such compounds, polypeptides and/or single-domain antibodies.

An immunogenic composition containing a Clostridium difficile (C. difficile) surface polysaccharide II (PSII) or an immunogenic portion thereof; and an α-galactosylceramide (α-GC) or analog or derivative thereof, which is able to bind to a CD1d glycoprotein, optionally containing a C. difficile TcdB C-terminal domain (CTD), or an immunogenic portion thereof, and/or an adjuvant. A method of treating, ameliorating, or inhibiting a C. difficile infection or a C. difficile-associated diarrhea in a subject by administering the immunogenic composition, particularly in subjects at risk for a C. difficile infection. A method of protecting a subject's gut microflora by administering the immunogenic composition or a composition containing α-GC and an alum adjuvant.

The invention provides a spleen regulating type B lymphocyte as well as a preparation method and application thereof. On one hand, the invention provides a spleen regulating type B lymphocyte, wherein the proportion of CD1d, CD5 and CD21/35 antibody positive regulating type B lymphocytes in the cell is more than 94.6%. The invention further provides a method for preparing the spleen regulating type B lymphocyte. The method for preparing the spleen regulating type B lymphocyte comprises the following steps: taking a spleen cell suspension, and marking with surface antibodies CD1d, CD5 and CD21/35; the labeled cells are sorted by fluorescence activated cell sorting. The third aspect of the invention provides application of the spleen regulating type B lymphocyte in preparation of a preparation for targeted colonization in bilateral kidneys. The fourth aspect of the invention provides application of the spleen regulating type B lymphocyte in preparation of a product for kidney protection.