1406 results about "Dendritic cell" patented technology

The present invention relates to methods and compositions for use in mediating an immunosuppressive reaction. The compositions of the invention comprise exosomes having immunosuppressive activity. Such exosomes may be derived from a variety of different cell types, including antigen presenting cells such as dendritic cells and macrophages. Prior to isolation of exosomes, the cells may be genetically engineered to express molecules capable of enhancing the immunosuppressive activity of said exosomes and/or may be exposed to one or more agents, such as cytokines or cytokine inhibitors, which are also capable of enhancing the immunosuppressive activity of exosomes. The present invention also relates to the use of such exosomes for the treatment of diseases and disorders associated with undesirable activation of the immune system. The present invention also includes exosomes isolated directly from serum that have been shown to be immunosuppressive.

Compounds for targeted immunotherapy, compositions comprising the compounds and use of the compounds in the treatment of diseases such as cancer are disclosed. The compounds having the structure of formula TM-Ln-AM, wherein TM is a targeting moiety, AM is an activating moiety that is capable of activating a human dendritic cell, NK cell, or tumor cell, or a combination thereof, Ln is a linker, and n is an integer selected from 0 and 1.

The present invention comprises compositions, methods, and devices for creating an stimulating an antigen-specific dendritic cell immune response. Devices and methods provide prophylactic and therapeutic immunity to subjects against cancer and infectious agents.

The present invention is directed to a composition and method which to treat diseases and to enhance a regulated immune response. More particularly, the present invention is drawn to compositions that are based on dendritic cells modified to express an inducible form of a co-stimulatory polypeptide.

A method is described whereby dendritic cells derived from the CD34+ and CD 34−hematopoietic cell lineages are directed to become programmable antigen presenting cells. The programmed cells may be pulsed with tumor cell RNA or tumor cell RNA expression products. The protocol provides for directing the maturation of dendritic cells to become antigen presenting cells. The protocol further provides for isolating tumor cell RNA from biopsy material that has been prepared in paraffin block storage. The directed dendritic cell is provided with a plurality of tumor markers by using tumor RNA in toto, the poly A+RNA fraction or the expression product of such RNA. Once activated the dendritic cells are incubated with T4 and T8 lymphocytes to stimulate and sensitize the T lymphocytes which upon introduction either into a donor host or a nondonor recipient will provide immune response protection.

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 present invention concerns methods and compositions for forming anti-cancer vaccine complexes. In preferred embodiments, the anti-cancer vaccine complex comprises an antibody moiety that binds to dendritic cells, such as an anti-CD74 antibody or antigen-binding fragment thereof, attached to an AD (anchoring domain) moiety and a xenoantigen, such as CD20, attached to a DDD (dimerization and docking domain) moiety, wherein two copies of the DDD moiety form a dimer that binds to the AD moiety, resulting in the formation of the vaccine complex. The anti-cancer vaccine complex is capable of inducing an immune response against xenoantigen expressing cancer cells, such as CD138^negCD20⁺ MM stem cells, and inducing apoptosis of and inhibiting the growth of or eliminating the cancer cells.

The present invention includes compositions and methods for increasing the effectiveness of antigen presentation using a DCIR-specific antibody or fragment thereof to which an antigen is attached that forms an antibody-antigen complex, wherein the antigen is processed and presented by a dendritic cell that has been contacted with the antibody-antigen complex.

Lentiviral vector particles comprising a Sindbis virus E2 glycoprotein variant and a lentiviral vector genome comprising a sequence of interest are provided. A lentiviral vector particle comprising: (a) an envelope comprising a Sindbis virus E2 glycoprotein variant; and (b) a lentiviral vector genome comprising a sequence of interest; wherein the E2 glycoprotein variant facilitates infection of dendritic cells by the lentiviral vector particle, and wherein the E2 glycoprotein variant has reduced binding to heparan sulfate compared to a reference sequence (HR strain).

The present invention includes compositions and methods for making and using a vaccine that includes a DC-specific antibody or fragment thereof to which an engineered Gag antigen is attached to form an antibody-antigen complex, wherein the Gag antigen is less susceptible to proteolytic degradation by eliminating one or more proteolytic sites or a DC-specific antibody or fragment thereof to which an engineered Nef antigen is attached to form an antibody-antigen complex, wherein the Nef antigen comprises one or more codon usage optimization that increase antibody-antigen complex secretion, or both, wherein the vaccine is able to elicit an HIV-specific T cell immune response to Gag p17, Gag p24, Nef and/or Cyclin D1.

The present invention relates to compositions comprising compounds which augment activated immune cells, such as T-cells, dendritic cells and natural killer ("NK") cells, and methods for the treatment or prevention of diseases and disorders, including cancer, inflammatory disorders, and infectious diseases, in a subject comprising the administration of said compositions to said subject. In particular, the present invention relates to methods for the treatment or prevention of diseases and disorders, including cancer, inflammatory disorders, and infectious diseases, in a subject comprising administrating to said subject one or more compounds that activate one or more cytokine receptors and one or more compounds that activate one or more co-stimulatory molecules expressed by activated immune cells. The present invention also relates to compositions and kits comprising a compound that activates one or more cytokine receptors and a compound that activates one or more co-stimulatory molecules expressed by activated immune cells.

Transcutaneous immunization can deliver antigen to the immune system through the stratum corneum without physical or chemical penetration to the dermis layer of the skin. This delivery system induces an antigen-specific immune response without the use of a heterologous adjuvant. Although perforation of intact skin is not required, superficial penetration or micropenetration of the skin can act as an enhancer; similarly, hydration may enhance the immune response. This system can induce antigen-specific immune effectors after epicutaneous application of a formulation containing one or more antigens. The formulation may initiate processes such as antigen uptake, processing, and presentation; Langerhans cell activation, migration from the skin to other immune organs, and differentiation to mature dendritic cells; contacting antigen with lymphocytes bearing cognate antigen receptors on the cell surface and their stimulation; and combinations thereof. Systemic and/or regional immunity may be induced. Immune responses that provide prophylactic and/or therapeutic treatments are preferred. Antigenic activities in the formulation may be found in the same molecule, two or more different molecules dissociated from each other, or multiple molecules in a complex formed by covalent or non-covalent bonds. For antigens which are proteinaceous, they may be provided in the formulation as a polynucleotide for transcutaneous genetic immunization. Besides simple application of a dry or liquid formulation to the skin, patches and other medical devices may be used to deliver antigen for immunization.

Methods and compositions for treating an infection or disease that results from (1) failure to elicit rapid T cell mediated responses, (2) induction of T cell exhaustion, T cell anergy or both, or (3) failure to activate monocytes, macrophages, dendritic cells and/or other APCs, for example, as required to kill intracellular pathogens. The method and compositions solve the problem of undesired T cell inhibition by binding to and blocking PD-1 to prevent or reduce inhibitory signal transduction, or by binding to ligands of PD-1 such as PD-L1, thereby preventing (in whole or in part) the ligand from binding to PD-1 to deliver an inhibitory signal. The immune response can be modulated by providing antagonists which bind with different affinity (i.e., more or less as required), by varying the dosage of agent which is administered, by intermittent dosing over a regime, and combinations thereof, that provides for dissociation of agent from the molecule to which it is bound prior to being administered again (similar to what occurs with antigen elicitation using priming and boosting). In some cases it may be particularly desirable to stimulate the immune system, then remove the stimulation.

This invention relates to methods of using human dendritic cells to present antigens for the induction of antigen-specific T cell-mediated immune responses. In particular, it relates to the isolation of dendritic cells from human blood, exposing the cells to antigens, co-culturing the antigen-pulsed dendritic cells with gammadelta-T cell receptor-positive-T cells (gammadelta-TCR<+> T cells) obtained from unprimed or weakly primed individuals for the stimulation of antigen-specific T cell proliferative and cytotoxic activities. The dendritic cell antigen presentation system described herein has a wide range of applications, including but not limited to, activation and expansion of large numbers of antigen-specific major histocompatibility complex-unrestricted T cells for use in adoptive cellular immunotherapy against infectious diseases and cancer.

The present invention provides an adjuvanting material, the adjuvanting material comprising a lipid dendritic cell targeting moiety to which is covalently linked a metal chelating group. Further, the present invention provides an immunogenic composition comprising (a) a lipid dendritic cell targeting moiety to which is covalently linked a metal chelating group; (b) an antigen comprising a metal affinity tag; and optionally (c) metal ions, whereby the antigen is linked to the lipid dendritic cell targeting moiety via the interaction between the metal affinity tag and the metal chelating group.

T cell immune responses are enhanced by presentation of antigen to CD8⁺ T cells using a chimeric nucleic acid immunogen or vaccine that links DNA encoding an antigen with DNA encoding a polypeptide that targets or translocates the antigenic polypeptide to which it is fused (immunogenicity-potentiating polypeptides or “IPP”). By inhibiting apoptosis in the vicinity of a T cell responses to such a nucleic acid immunogen, even more potent immune responses are attained. The present strategy prolongs the survival of DNA-transduced cells, including dendritic cells (DCs), thereby enhancing the priming of antigen-specific T cells and increase potency. Co-delivery of DNA encoding an inhibitor of apoptosis, including (a) BCL-xL, (b) BCL-2, (c) XIAP, (d) dominant negative caspase-9, or (e) dominant negative caspase-8, or (f) serine protease inhibitor 6 (SPI-6) which inhibits granzyme B, with DNA encoding an antigen, prolongs the survival of transduced DCs and results in significant enhancement of antigenspecific T cell immune responses that provide potent antitumor effects. Thus, co-administration of a DNA vaccine encoding antigen linked to an IPP along with one or more DNA constructs encoding an anti-apoptotic protein provides a novel way to enhance vaccine potency.