127 results about "CD86" patented technology

The present invention provides compositions comprising one or more RNAi agents (e.g., siRNAs, shRNAs, or RNAi vectors) for the treatment of conditions and diseases mediated by (e.g., featuring IgE-mediated hypersensitivity), as well as systems for identifying RNAi agents effective for this purpose. The compositions are suitable for the treatment of allergic rhinitis and / or asthma. In certain embodiments of the invention the RNAi agent is targeted to a transcript that encodes a protein selected from the group consisisting of the FCεRIα chain, the FCεRIβ chain, c-Kit, Lyn, Syk, ICOS, OX40L, CD40, CD80, CD86, Re1A, Re1B, 4-1BB ligand, TLR1, TLR2, TLR3, TLR4, TLR5, TLR6, TLR7, TLR8, TLR9, CD83, SLAM, common γ chain, and COX-2. In addition, the invention provides RNAi agent / delivery agent compositions and methods of use. In certain embodiments of the invention compositions comprising an RNAi agent are delivered by the respiratory route.

A method and composition for inducing human dendritic cells to a condition of reduced capacity for antigen-specific activation of T cells, and, in mature dendritic cells, increased production of extracellular IL-10 is disclosed. A population of dendritic cells is exposed to a substantially uncharged antisense compound, including partially positively charged, containing 12-40 subunits and a base sequence effective to hybridize to an expression-sensitive region of a preprocessed or processed human CD86 transcript identified, in its processed form, by SEQ ID NO:33, to form a duplex structure between said compound and transcript having a Tm of at least 45° C. Formation of the duplex blocks expression of full-length CD86 in said cells, which in turn leads to reduced capacity for antigen-specific activation of T cells, and, in mature dendritic cells, increased production of extracellular IL-10.

The present invention is directed to methods and kits based, at least in part, on the identification of allele-specific responsiveness or non-responsiveness to glatiramer acetate for the treatment of immune disorders, such as relapsing-remitting multiple sclerosis. The allele-specific responsiveness or non-responsiveness is based on polymorphisms in the following genes, CTSS, MBP, TCRB, CD95, CD86, IL-1R1, CD80, SCYA5, MMP9, MOG, SPP1 and IL-12RB2.

It has been found that dendritic cells can be prepared which cannot mature. These cells can provide signal 1 to T cells but cannot provide co-stimulatory signal 2. T cells which are stimulated by the permanently immature dendritic cells therefore anergise, so the dendritic cells are tolerogenic rather than immunogenic. The cells are generally CD40−ve, CD80−ve and CD86−ve, and remain so when stimulated by inflammatory mediators such as lipopolysaccharide. The cells can be prepared conveniently by the culturing adherent embryonic stem cells in the presence of GM-CSF.

The present invention relates to the identification of molecules, which are specific to CD80 and CD86 antigens. Also preferably, such antibodies are capable of inhibiting the binding of CD28 and CTLA4 to those receptors. Those molecules are able to inhibit T cell mediated immune reactions.

The present invention provides soluble CTLA4 mutant molecules which bind with greater avidity to the CD80 and / or CD86 antigen than wild type CTLA4 or non-mutated CTLA4Ig. The soluble CTLA4 molecules have a first amino acid sequence comprising the extracellular domain of CTLA4, where certain amino acid residues within the S25-R33 region and M97-G107 region are mutated. The mutant molecules of the invention may also include a second amino acid sequence which increases the solubility of the mutant molecule.

AS-oligonucleotides are delivered in microsphere form in order to induce dendritic cell tolerance, particularly in the non-obese-diabetic (NOD) mouse model. The microspheres incorporate antisense (AS) oligonucleotides. A process includes using an antisense approach to prevent an autoimmune diabetes condition in NOD mice in vivo and in situ. The oligonucleotides are targeted to bind to primary transcripts CD40, CD80, CD86 and their combinations.

This disclosure provides a multi-specific fusion protein composed of a CD86 antagonist binding domain and another binding domain that is an IL-10 agonist, an HLA-G agonist, an HGF agonist, an IL-35 agonist, a PD-1 agonist, a BTLA agonist, a LIGHT antagonist, a GITRL antagonist or a CD40 antagonist. The multi-specific fusion protein may also include an intervening domain that separates the other domains. This disclosure also provides polynucleotides encoding the multi-specific fusion proteins, compositions of the fusion proteins, and methods of using the multi-specific fusion proteins and compositions.

The present invention relates to a transplant rejection in an animal suppressed by administration of an antibody directed at a cell surface antigen selected from the group consisting of CD4, CD8, CD154, LFA-1, CD80, CD86 and ICAM-1, preferably an anti-CD4 antibody, together with a non-cellular protein antigen to generate in the animal a population of regulatory T-lymphocytes; reactivating said population of regulatory T-lymphocytes by further administration to the animal of the non-cellular protein antigen; and transplanting said organ or tissue whilst said population of regulatory T-lymphocytes is activated. Regulatory T cells can be generated ex vivo by culturing T cells with an antibody directed at a cell surface antigen selected from the group consisting of CD4, CD8, CD154, LFA-1, CD80, CD86 and ICAM-1, in the presence of cells that present either alloantigen or a non-cellular protein antigen. Ex vivo generated T-lymphocytes can be used as an alternative method of overcoming transplant rejection or in combination with the in vivo method. A similar approach can be adopted for the treatment of autoimmune conditions.

The invention discloses a method for amplification and activation of NK cells by K562 cells. The method comprises that through synergism of K562 cells transfected by transmembrane interleukin 21, CD14, CD19, CD86 and CD137, and low-concentration interleukin 2, NK cells are subjected to directed amplification and activation. Compared with the existing similar compounds, the compound provided by the invention has a stronger lymphocyte amplification and activation capability and higher efficiency. The method has wide prospects in immunological therapy.

The present invention is directed to methods and kits based, at least in part, on the identification of allele-specific responsiveness or non-responsiveness to glatiramer acetate for the treatment of autoimmune disorders, such as relapsing-remitting multiple sclerosis. The allele-specific responsiveness or non-responsiveness is based on polymorphisms in the following genes, CTSS, MBP, TCRB, CD95, CD86, IL-1R1, CD80, SCYA5, MMP9, MOG, SPP1 and IL-12RB2.

In this invention, the inventor discloses that naturally occurring IgM anti-lymphocyte antibodies bind to chemokine and non-chemokine receptors on lymphocytes and other cells, and downmodulate certain receptors including CD4 and CD2 on T cells and CD80 and CD86 on macrophages. The inventor also discloses that such antibodies (i) inhibit HIV-1 and other viruses from infecting cells (ii) inhibits activation and proliferation of T lymphocytes (iii) inhibits cytokine and chemokine production (iv) inhibits inflammatory processes, and (v) enhances death of malignant cells. This art or invention is novel in that the antibodies described herein are “naturally occurring” i.e. develop in absence of deliberate immunization and secondly these antibodies are distinct from disease causing autoantibodies in that these naturally occurring antibodies are polyreactive with low binding affinity.

A method and composition for inducing human dendritic cells to a condition of reduced capacity for antigen-specific activation of T cells, and, in mature dendritic cells, increased production of extracellular IL-10 is disclosed. A population of dendritic cells is exposed to a substantially uncharged antisense compound containing 12-40 subunits and a base sequence effective to hybridize to an expression-sensitive region of a preprocessed or processed human CD86 transcript identified, in its processed form, by SEQ ID NO:33, to form a duplex structure between said compound and transcript having a Tm of at least 45° C. Formation of the duplex blocks expression of full-length CD86 in said cells, which in turn leads to reduced capacity for antigen-specific activation of T cells, and, in mature dendritic cells, increased production of extracellular IL-10.

The present invention provides use of soluble CTLA4 mutant molecules which bind with greater avidity to the CD80 and / or CD86 antigen than wild type CTLA4 or non-mutated CTLA4Ig in the treatment of immune disorders associated with graft transplantation.

Polynucleotides encoding at least one immunizing antigen whose expression is controlled by a promoter derived from a gene encoding a co-stimulatory molecule are provided. The polynucleotides may also encode adjuvants. Compositions comprising at least one immunizing agent and at least one cytokine that enhance dendritic cell stimulation and / or survival are also provided. Methods for eliciting an immune response against the immunizing agent are also provided. The method includes the steps of administering the polynucleotides and, optionally, co-administering an adjuvant.

The invention discloses a method for efficiently amplifying NK cells, in particular to a method for efficiently amplifying NK cells using K562 engineered cells of high expression membrane proteins CD19, CD137L, CD86, CD64 and transmembrane protein IL- 21 and combining with human IL-2 mutants. The method has the advantages of simple operation, low cost, large number of obtained NK cells, high purity and good killing effect; the method is suitable for large-scale preparation of the NK cells and lays a good foundation for the application of NK cell adoptive immunotherapy in clinical practice.

In some embodiments, compositions and methods relating to isolated artificial antigen presenting cells (aAPCs) are disclosed, including aAPCs comprising a myeloid cell transduced with one or more viral vectors, such as a MOLM-14 or a EM-3 myeloid cell, wherein the myeloid cell endogenously expresses HLA-AB / C, ICOS-L, and CD58, and wherein the one or more viral vectors comprise a nucleic acid encoding CD86 and a nucleic acid encoding 4-1BBL and / or OX40L and transduce the myeloid cell to express CD86 and 4-1BBL and / or OX40L proteins. In some embodiments, methods of expanding tumor infiltrating lymphocytes (TILs) with aAPCs and methods of treating cancers using TILs after expansion with aAPCs are also disclosed.

The invention discloses an artificial antigen submitting cell and preparing method, which comprises the following steps: choosing human chronic granular leukocyte leukemia bacterial strain K562 cell as carrier; transfer-dying and expressing eucaryon expressing carrier of CD32a; expressing CD32 molecular on the surface of K562 cell stably through G418 screening and flowed cell sorting device sorting; forming K32 cell; producing eucaryon expressing carrier of double expressing CD86 and 4-1BBL co-simulating signal; proceeding homomycin screen and sort with flowed cell device for the K32 cell; getting stable expression K32 cell of CD86 and 4-1BBL molecule; getting the end product. This invention possesses low cost and good repeatability, which can inhibit die effectively.

A chimeric protein expressed from a transgene tranduced into a mammalian tumor cell and method of using the chimeric protein for cancer treatment. The chimeric protein comprises an effector and an anchor, which are linked by a spacer. The chimeric protein, when expressed and exposed on the tumor cell surface in vivo can activate T cells, which further lead to lysis of the tumor cells. The anti-tumor effects can be enhanced by co-expression of certain co-stimulators, such as CD80 or CD86.

The present invention provides soluble CTLA4 mutant molecules which bind with greater avidity to the CD80 and / or CD86 antigen than wild type CTLA4 or non-mutated CTLA4Ig. The soluble CTLA4 molecules have a first amino acid sequence comprising the extracellular domain of CTLA4, where certain amino acid residues within the S25-R33 region and M97-G107 region are mutated. The mutant molecules of the invention may also include a second amino acid sequence which increases the solubility of the mutant molecule.

A peptide according to the present invention can perform a function identical or similar to the function of natural CTLA-4 and has an excellent degree of skin penetration due to a small size. The peptide according to the present invention effectively binds to antigen presenting cell surface proteins (CD80 and CD86) to inhibit activity of T cells and thus is capable of inhibiting the expression of inflammatory cytokines (for example, IL-2 and IFN-γ). As a result, a composition comprising the peptide according to the present invention exhibits excellent effects in terms of preventing, treating, or improving Th1-mediated immune diseases. Therefore, the superior activity and stability of the peptide according to the present invention can be useful when applied to medicine, quasi-drugs, and cosmetics.

This disclosure provides a multi-specific fusion protein composed of a CD86 antagonist binding domain and another binding domain that is an IL-10 agonist, an HLA-G agonist, an HGF agonist, an IL-35 agonist, a PD-1 agonist, a BTLA agonist, a LIGHT antagonist, a GITRL antagonist or a CD40 antagonist. The multi-specific fusion protein may also include an intervening domain that separates the other domains. This disclosure also provides polynucleotides encoding the multi-specific fusion proteins, compositions of the fusion proteins, and methods of using the multi-specific fusion proteins and compositions.