208 results about "Costimulatory Molecule" patented technology

Chimeric T cell receptors (TCR) are provided that combine, in a single chimeric species, the intracellular domain of CD3 ζ-chain, a signaling region from a costimulatory protein such as CD28, and a binding element that specifically interacts with a selected target. When expressed, for example in T-lymphocytes from the individual to be treated for a condition associated with the selected target, a T cell immune response is stimulated in the individual to the target cells. The chimeric TCR's are able to provide both the activation and the co-stimulation signals from a single molecule to more effectively direct T-lymphocyte cytotoxicity against the selected target and T-lymphocyte proliferation.

Chimeric T cell receptors (TCR) are provided that combine, in a single chimeric species, the intracellular domain of CD3 zeta-chain, a signaling region from a costimulatory protein such as CD28, and a binding element that specifically interacts with a selected target. When expressed, for example in T-lymphocytes from the individual to be treated for a condition associated with the selected target, a T cell immune response is stimulated in the individual to the target cells. The chimeric TCR's are able to provide both the activation and the co-stimulation signals from a single molecule to more effectively direct T-lymphocyte cytotoxicity against the selected target and T-lymphocyte proliferation.

The invention provides isolated nucleic acids molecules, designated B7-4 nucleic acid molecules, which encode novel B7-4 polypeptides. The invention also provides antisense nucleic acid molecules, recombinant expression vectors containing B7-4 nucleic acid molecules, host cells into which the expression vectors have been introduced, and nonhuman transgenic animals in which a B7-4 gene has been introduced or disrupted. The invention still further provides isolated B7-4 proteins, fusion proteins, antigenic peptides and anti-B7-4 antibodies. Diagnostic, screening, and therapeutic methods utilizing compositions of the invention are also provided.

Provided are methods of reducing the size of a tumor or inhibiting the growth of cancer cells in an individual or inhibiting the development of metastatic cancer by administering an effective amount of a soluble form of a co-stimulatory molecule from an antigen presenting cell and by reducing the activity of immunoregulatory T cells in the individual. Methods of reduction in the activity of immunoregulatory T cells involve removing them ex vivo or depleting or inactivating them in vivo. Also provided are cancer therapeutic compositions comprising a soluble form of a co-stimulatory molecule from an antigen presenting cell and an antibody specific for an intracellular antigen.

The present invention is a recombinant vector encoding and expressing at least three or more costimulatory molecules. The recombinant vector may additionally contain a gene encoding one or more target antigens or immunological epitope thereof. The synergistic effect of these costimulatory molecules on the enhanced activation of T cells is demonstrated. The degree of T-cell activation using recombinant vectors containing genes encoding three costimulatory molecules was far greater than the sum of recombinant vector constructs containing one costimulatory molecule and greater than the use of two costimulatory molecules. Results employing the triple costimulatory vectors were most dramatic under conditions of either low levels of first signal or low stimulator to T-cell ratios. This phenomenon was observed with both isolated CD4+ and CD8+ T cells. The recombinant vectors of the present invention are useful as immunogenes and vaccines against cancer and pathogenic micro-organisms, and in providing host cells, including dendritic cells and splenocytes with enhanced antigen-presenting functions.

The present invention is a recombinant vector encoding and expressing at least three or more costimulatory molecules. The recombinant vector may additionally contain a gene encoding one or more target antigens or immunological epitope thereof. The synergistic effect of them costimulatory molecules on the enhanced activation of T cells is demonstrated. The degree of T-cell activation using recombinant vectors containing genes encoding three costimulatory molecules was far greater than the sum of recombinant vector constructs containing one costimulatory molecule and greater that the use of two costimulatory molecules. Results employing the triple costimulatory vectors were most dramatic under conditions of either low levels of first signal or low stimulator to T-cell ratios. This phenomenon was observed with both isolated CD4+and CD8+T cells. The recombinant vectors of the present invention are useful as immunogenes and vaccines against cancer and pathogenic micro-organisms, and in providing host cells, including dendritic cells and splenocytes with enhanced and antigen-presenting functions.

The field of the present invention relates to genetically engineered fusion molecules, methods of making said fusion molecules, and uses thereof in anti-tumor immunotherapies. More specifically, the present invention relates to engineered fusion molecules consisting of a tumor targeting moiety fused with one or more costimulatory molecules / chemokines / cytokines.

The invention relates to a chimeric antigen receptor with stable antigen binding units. The chimeric antigen receptor comprises the extracellular antigen binding units, trans-membrane domains and intracellular co-stimulation signal domains. The antigen binding units can be stably expressed as compared with specific tumor targets and comprise heavy chains and light chains which are connected with one another by hinges of SEQ ID NO.2 (sequence identity number.2) amino acid sequence codes. The invention further relates to cells for expressing the receptor and application of the receptor.

Compositions are provided that are targeted to tumors or tumor-associated neovasculature and enhance the function of tumor-infiltrating T cells. The compositions include fusion proteins that contain a T cell binding domain and a tumor / tumor-associated neovasculature targeting domain. The fusion proteins optionally contain a peptide / polypeptide linker domain and a domain that mediates dimerization or multimerization. The T cell binding domain can be a costimulatory molecule. Methods for using the fusion proteins to enhance an immune response are provided. Therapeutic uses for the disclosed compositions include the induction of tumor immunity.

The present invention provides adeno-associated viral (AAV) vectors encoding an angiostatin protein ("AAV-angiostatin vector") and / or a costimulatory molecule B7.1 ("AAV-B7.1 vector"). The AAV-angiostatin vector can be administered to a subject, alone or in combination, sequentially or simultaneously, with a AAV-B7.1 vector for treatment, management or prevention of metastatic tumors. Pharmaceutical compositions and vaccines comprising the AAV-angiostatin vector and / or the AAV-B7.1 vector and methods of manufacturing are also described. Administration of AAV-angiostatin and AAV-B7.1 vectors by intraportal and muscular injections are also provided.

Methods of enhancing the efficacy of antibody-directed cellular cytotoxicity (ADCC) for therapy directed to killing of tumor cells are disclosed. Cancer specific cell surface antigens are bound by monoclonal antibodies, thereby stimulating a cytotoxic T cell response characterized by an upregulation of cell surface expression of costimulatory molecules on the T cell. The ADCC response is augmented by the subsequent administration of a second antibody that is an agonist of the costimulatory molecule.

The present invention relates to novel modified CEA agonist (or antagonist) peptides, polypeptides and proteins containing a modified epitope therein, nucleic acids coding therefor, vectors comprising said nucleic acids, mixtures and compositions of the aforementioned agents, and their advantageous use in generating CEA-specific immune responses and / or in the treatment of cancers and the present invention further relates to the foregoing combined with one or more costimulatory molecules.

The invention relates to the technical field of adipose mesenchymal stem cells in the technical field of cell therapy, in particular to a method for enhancing an immune regulating function and a migration capacity of adipose mesenchymal stem cells. Primary culture and secondary culture are performed to the adipose mesenchymal stem cells obtained through separation, and then short-time culture is performed by using culture medium containing low-concentration TLR3 activator Poly(I:C). After Poly(I:C) co-stimulation culture is performed, the obtained adipose mesenchymal stem cells with a brand new phenotype have a stronger migration capacity, the levels of secreting cytokine and chemotactic factor are changed and a stronger immunosuppressive function is reflected on the whole.

The present invention provides for a method of using heat shock proteins (HSPs) to amplify the immune response initiated by a vaccine. HSPs can be introduced into a subject before, concurrently, or after the administration of a vaccine. The HSPs can also be used to activate antigen presenting cells which are then introduced into a subject in conjunction with a vaccine. The HSPs used in the methods of the invention can be unbound or can be covalently or noncovalently bound to a peptide that is unrelated to the vaccine. The subject is preferably mammalian, and most preferably human. It is shown by way of example herein that HSPs induces secretion of cytokines and surface expression of antigen-presenting and co-stimulatory molecules. The invention also encompasses methods of treatment and prevention of cancer and infectious diseases in a subject.

The present invention provides for a method of using heat shock proteins (HSPs) to amplify the immune response initiated by a vaccine. HSPs can be introduced into a subject before, concurrently, or after the administration of a vaccine. The HSPs can also be used to activate antigen presenting cells which are then introduced into a subject in conjunction with a vaccine. The HSPs used in the methods of the invention can be unbound or can be covalently or noncovalently bound to a peptide that is unrelated to the vaccine. The subject is preferably mammalian, and most preferably human. It is shown by way of example herein that HSPs induces secretion of cytokines and surface expression of antigen-presenting and co-stimulatory molecules. The invention also encompasses methods of treatment and prevention of cancer and infectious diseases in a subject.

Disclosed is a pharmaceutical composition for treating immunological disorders by inhibiting the activation of T lymphocytes, comprising, as active ingredients, two or more selected from the group consisting of a substance capable of blocking binding of an MHC (Major Histocompatibility Complex) Class II molecule and a receptor thereof, a substance capable of blocking binding of a costimulatory molecule and a receptor thereof, a substance capable of blocking binding of an adhesion molecule and a receptor thereof, and a substance capable of blocking binding of a cytokine and a receptor thereof.

The present invention provides a recombinant pox virus composition comprising a nucleic acid sequence encoding chemokines as costimulatory molecules. The present invention further provides a host cell, a host animal, and a pharmaceutical composition comprising the recombinant pox virus composition. Also provided is a method for treating or preventing a neoplasm or infectious disease in a subject, using the pox virus composition and / or an SLC agent. Additionally, the present invention provides a method for promoting the proliferation of a CD4 T cell, comprising administering to the cell an SLC agent in an amount effective to directly promote the proliferation of the cell. Finally, the present invention provides a method for treating or preventing a neoplasm or infectious disease in a subject using cultured CD4 T cells.

Aptamer oligonucleotides specifically bind to the DNA binding site of proteins such as Sp1 and Sp1-related proteins which regulate the genes which encode costimulatory molecules such as CD28 and cytokines such as IL-2 and GMCSF. The oligonucleotides compete with the DNA-binding sites of regulatory proteins which specifically regulate molecules to modulate T-cell activation. This serves to modulate gene expression by preventing transcription of the gene. Aptamers are administered to provide therapies for diseases which involve aberrant T-cell activation such as psoriasis, Type I (insulin-dependent) diabetes mellitus, multiple sclerosis, autoimmune uveitis, rheumatoid arthritis, systemic lupus erythematosus, inflammatory bowel disease (Crohn's and ulcerative colitis), and septic shock and to regulate normal T-cell activation such as in allograft rejection.

The invention relates to a chimeric antigen receptor, nucleic acid encoding the same, cells expressing the chimeric antigen receptor, and application of the chimeric antigen receptor in preparing drugs for treating tumors. The chimeric antigen receptor comprises at least one extracellular structural domain, an optional membrane spanning structural domain and at least one intracellular co-stimulation signal transduction structural domain, wherein the extracellular structural domains involve CD19 antigen recognition binding structural domains. The chimeric antigen receptor has a longer in-vivo survival period after being subjected to humanized transformation, and the complete remission period of a patient can also be prolonged accordingly.

Attenuated, replication-deficient viruses such as vaccinia viruses are used to deliver an exogenous viral, bacterial, parasitic or tumor antigen to an epidermal tissue such as the skin, lungs or gastrointestinal tract, which has been mechanically disrupted, in an amount effective to elicit or stimulate a cell mediated immune response. The epidermal tissue may be mechanically disrupted by a device such as a scarification needle or an abrader device. The epidermis may be mechanically disrupted prior to, at the same time, or immediately after the administration of the vaccine. The vaccine can be used to induce immunity against a pathogen, such as a virus, bacteria, or parasite, or against a cancer in a subject that has or is at risk of developing cancer. In some embodiments a co-stimulatory molecule, a growth factor, an adjuvant and / or a cytokine is administered before, with or after the viral vaccine. In some embodiments, the co-stimulatory molecule is co-expressed with the antigen by the virus.

The present invention is a recombinant vector encoding and expressing at least three or more costimulatory molecules. The recombinant vector may additionally contain a gene encoding one or more target antigens or immunological epitope thereof. The synergistic effect of these costimulatory molecules on the enhanced activation of T cells is demonstrated. The degree of Tell activation using recombinant vectors containing genes encoding three costimulatory molecules was far greater than the sum of recombinant vector constructs containing one costimulatory molecule and greater than the use of two costimulatory molecules. Results employing the triple costimulatory vectors were most dramatic under conditions of either low levels of first signal or low stimulator to T-cell ratios. This phenomenon was observed with both isolated CD4+ and CD8+ T cells. The recombinant vectors of the present invention are useful as immunogenes and vaccines against cancer and pathogenic micro-organisms, and in providing host cells, including dendritic cells and splenocytes with enhanced antigen-presenting functions.

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.

A therapeutic composition or a vaccine comprising tumor membrane-anchored cytokines or other immunostimulatory or costimulatory molecules are provided. The therapeutic composition or a tumor vaccine can be used for treating a tumor or other disease such as autoimmune disorder, viral diseases, bacterial diseases, parasitic diseases, and transplant rejection.

The invention relates to the field of tumor cellular immunotherapy, and in particular relates to a recombinant lentivirus and application thereof. The recombinant lentivirus comprises a chimeric antigen receptor, wherein the chimeric antigen receptor mainly comprises signal peptide, an antigen recognition domain, a transmembrane domain, an intracellular co-stimulation signal transduction domain and a CD3 zeta signal transduction domain which are serially connected; the intracellular co-stimulation signal transduction domain mainly comprises a human TLR2 (Toll Like Receptor 2) intracellular domain. A GPC3 CAT T (Glypican 3 CAT T) cell prepared from the recombinant lentivirus has an intense cell killing effect on liver cancer cells, a Th1 cell factor can be highly expressed, a tumor killing effect caused by non-CAR T (Chimeric Antigen Receptor T) cell can be stimulated to the maximum extent, escape and potential reoccurrence risk of GPC 3-tumor cells can be effectively prevented, the tumor cells can be killed by T cells expressing the chimeric antigen receptor, normal tissue can be slightly damaged, a tumor immunosuppression micro environment can be broken through, and thus a relatively good treatment effect on solid tumor can be achieved.

The invention aims to provide an efficient culture method of CIK cells. The prepared CIK cell has the characteristics of high multiplication speed, large cell quantity, high cell viability, high killing capacity on cancer cells and the like. The efficient culture method mainly characterized in that a culture flask coated with laminin and fibronectin is used for culturing PBMCs (peripheral blood mononuclear cells), and the cells can be in a half-adherence state by means of the absorption effect of the two kinds of protein, accordingly, the cells can be stimulated by various factors, and the two kinds of protein can promote CIK cell multiplication; and with the adoption of an anti-CD28 monoclonal antibody, the co-stimulation signal of a T cell subset in the CIK cells can be stimulated, and the activation of the CIK cells is promoted. So far, a research report on jointly using laminin, fibronectin and the anti-CD28 monoclonal antibody to prepare the CIK cells is absent. The method for increasing the cell number and improving the killing activity by adding the three factors during preparation of the CIK cells is firstly provided.

The present invention provides novel virus vaccines with augmented, e.g., enhanced and / or extended immunogenicity. The virus vaccines of the invention comprise an envelope-bound immunomodulatory protein, e.g., a cytokine, chemokine or costimulatory molecule. The immunomodulatory protein serves as an adjuvant to augment, e.g., enhance or extend the immunogenicity of the virus vaccine, thereby augmenting, e.g., enhancing or extending immune response to the virus when administered to a subject.

Provided are methods of reducing the size of a tumor or inhibiting the growth of cancer cells in an individual or inhibiting the development of metastatic cancer by administering an effective amount of a soluble form of a co-stimulatory molecule from an antigen presenting cell and by reducing the activity of immunoregulatory T cells in the individual. Methods of reduction in the activity of immunoregulatory T cells involve removing them ex vivo or depleting or inactivating them in vivo. Also provided are cancer therapeutic compositions comprising a soluble form of a co-stimulatory molecule from an antigen presenting cell and an antibody specific for an intracellular antigen.

The invention provides a magnetism, pH (potential of hydrogen) and temperature co-stimulation response hydrogel pre-radiation synthetic method, belongs to the technical field of nuclear biology, and solves the technical problems of low existing nano-composite hydrogel environment stimulation response rate and the like. The synthetic method includes the steps: 1) injecting temperature sensitive monomer solution into PE (polyethylene) sealing bag, leading in N2, and performing pre-radiation cross-linking reaction under electron beams; 2) placing macromolecule irradiation sensitizing agents, natural polysaccharide, pH conditioning agents, magnetic nano-particles and distilled water or deionized water into a bottle, and the heating the bottle; 3) slowly adding a mixed solution system acquiredin the step 2) into the temperature sensitive monomer solution acquired in the step 1), performing uniformly ultrasonic stirring, and leading in the N2; 4) injecting the mixed system acquired in the step 3) into the PE sealing bag, and performing radiation cross-linking reaction under electron beams again. The method has the advantages that the comprehensive performances of nano-composite hydrogelare optimized and the like.