32 results about "Antigen uptake" patented technology

The present invention provides methods for combining computational methods for modulating protein immunogenicity with computational methods for identifying sequences with desired structural and functional properties. More specifically, the methods of the present invention may be used to identify modifications that increase or decrease the immunogenicity of a protein by affecting antigen uptake, MHC binding, T-cell binding, or antibody binding, while retaining or enhancing functional properties.

An objective of the present invention is to provide methods for facilitating antigen-binding molecule-mediated antigen uptake into cells, methods for facilitating the reduction of antigen concentration in plasma, methods for increasing the number of antigens to which a single antigen-binding molecule can bind, methods for improving pharmacokinetics of antigen-binding molecules, antigen-binding molecules improved for facilitated antigen uptake into cells, antigen-binding molecules capable of facilitating the reduction of antigen concentration in plasma, antigen-binding molecules capable of repeatedly binding to antigens, antigen-binding molecules with improved pharmacokinetics, pharmaceutical compositions comprising such an antigen-binding molecule, and methods for producing those described above. The present inventors discovered that antigen uptake into cells is facilitated by an antibody having human FcRn-binding activity at the plasma pH and a lower antigen-binding activity at the early endosomal pH than at the plasma pH; such antibodies can increase the number of antigens to which a single antibody molecule can bind; the reduction of antigen in plasma can be facilitated by administering such an antibody; and antibody pharmacokinetics can be improved by using such antibodies.

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.

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. Use of skin-active adjuvants is preferred. 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 antigen and adjuvant. 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 result in prophylaxis and/or therapeutic treatments are preferred. Antigen and adjuvant 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 and adjuvants which are proteinaceous, they may be provided in the formulation as a polynucleotide for transcutaneous genetic immunization. Besides simple application of a liquid formulation, patches or other medical devices may be used to deliver antigen for immunization.

The invention relates to an antigen and TLR agonist targeting co-loaded cationic phospholipid-polymer hybrid nanoparticle vaccine adjuvant, and a preparation method and an application thereof. A hydrophobic inner core is encapsulated with a TLR7 agonist, a phospholipid layer is encapsulated with a TLR4 agonist, an antigen is adsorbed by cationic phospholipids in the phospholipid layer, and ligation of a mannose ligand makes the vaccine adjuvant like a specific targeting antigen to have the dendritic cell presenting ability, so the DC cell intake and the maturation promoting effect are enhanced; and the antigen is protected by hybridized nanoparticles, the antigen uptake by DC cells is improved, immune response after antigen stimulation is significantly enhanced by the TLR agonist, and thecross-presentation of the antigen is significantly improved, so vaccine adjuvant has a strong potent T cell killing effect, can induce cytokine secretion, has a long-acting memory T cell response, andhas an excellent prevention effect on tumors.

Methods and compositions for generating novel nucleic acid molecules through targeted spliceosomal mediated trans-splicing that result in expression of an immunogenic polypeptide. The invention includes pre-trans-splicing molecules (PTMs) designed to interact with a target precursor messenger RNA molecule (target pre-mRNA) and mediate a trans-splicing reaction resulting in the generation of a novel chimeric RNA molecule (chimeric RNA) capable of encoding the immunogenic polypeptide, recombinant vector systems capable of expressing the PTMs of the invention, and cells expressing said PTMs. The target pre-mRNA are those encoding proteins that function in antigen uptake, antigen presentation and chaperoning. The methods of the invention encompass contacting the PTMs of the invention with a target pre-mRNA, under conditions in which a portion of the PTM is trans-spliced to a portion of the target pre-mRNA to form a chimeric mRNA molecule capable of encoding an immunogenic polypeptide.

The invention relates to a cationic liposome-protamine-mRNA tumor vaccine and a preparation method and an application method thereof. According to the tumor vaccine, a cationic liposome-protamine compound is used as a delivery carrier and adjuvant of mRNA, wherein the mass ratio of the cationic liposome to protamine to mRNA is 5:1: 1 to 15: 2:1, and the optimal mass ratio is preferably 10:1:1; theparticle size of the constructed cationic liposome-protamine-mRNA tumor vaccine is 50 to 800nm; the Zeta potential is 10 to 60mv; and the encapsulation efficiency is 70% to 95%. The cationic liposome-protamine-mRNA tumor vaccine prepared by the invention can effectively promote antigen uptake of APCs, induce DC stimulation and maturation, promotes secretion of cytokines and cause anti-tumor immune response. The tumor vaccine is used for immunotherapy through intramuscular and subcutaneous injection or nasal mucosa administration, wherein nasal mucosa administration can show a more excellent tumor treatment effect. The tumor vaccine has a wide application prospect in the aspect of tumor treatment.

The invention covers the use of certain classes of lipids including cationic lipids in ex-vivo dendritic cell therapies. The cationic lipids enhance antigen uptake, processing and presentation of the processed antigens by dendritic cells to CD8+ and CD4+ T-cells via the MHC classes I and II presentation pathways respectively. Antigen uptake via cationic lipid by dendritic cells result in significant lowering of the population of the immune suppressive regulatory T cells in the tumors and a significant increase of the tumor targeting cytotoxic T-cells. Loss of regulatory T cells and increase of tumor specific cytotoxic cells are conducive to effective elimination of the tumors.

The invention relates to a mannose modified co-loaded antigen and a double immuno-agonist phospholipid hybrid polymer vesicle as well as a preparation method and application thereof. A vaccine carriertakes an amphiphilic triblock copolymer as material, OVA is loaded in the hydrophilic inner cavity, IMQ is loaded in the hydrophobic membrane layer, DOTAP cationic layer is fitted with MPLA, and cationic lipid outer layer adsorbs outer layer OVA; phospholipid with reactive group is introduced to pass the targeted mannose ligand through covalently linked to the PEG-active distal end of the polymer-loaded vesicle surface, integrating the functions of active targeting of tumors, co-delivery of antigens and adjuvants and the like; the vesicle has the characteristics of small particle size, good dispersion, high antigen loading and good biocompatibility, etc., which can promote antigen uptake, DC activation and maturation, antigen cross-presentation, antigenic lymph node migration, lymphocyteactivation, effector T cell immune response, CD8<+> T and CD4<+> T cell responses, and memory T cells immune response.

The invention discloses application of chrysin in preparation of medicaments for treating autoimmune diseases. Experimental results show that the chrysin can inhibit differentiation of human immune dendritic cells (DC) and maturity of LPS (lipopolysaccharide)-activated human immune DC, can inhibit the antigen uptake capabilities of the immature DC and the antigen presenting capabilities of the mature DC and can inhibit T cell proliferation reactions stimulated by the DC. In particular, the chrysin can reduce the average score, the highest score and the total score of clinical scores of experimental autoimmune encephalomyelitis of mice and can relieve myelitis cell infiltration and demyelination in spinal cords. Thus, the medicament inhibiting immune systems is expected to become the medicament for treating such autoimmune inflammatory diseases as multiple sclerosis, neuromyelitis optica and acute disseminated encephalomyelitis clinically.

Dendritic cells play a critical role in antigen-specific immune responses. Materials and methods are provided for treating disease states, including cancer and autoimmune disease, by facilitating or inhibiting the migration or activation of antigen-presenting dendritic cells. In particular, chemokines are used to initiate, amplify or modulate an immune response. In one embodiment, chemokines are used to attract dentritic cells to the site of antigen delivery. An increase number of dendritic at the site of antigen delivery means more antigen uptake and a modified immune response.

The invention relates to the fields of biotechnology and medicine, and provides a dendritic cell (DC) with ATPIF1 gene knock-down expression. The ATPIF1 gene is knocked down in the dendritic cell, sothat the antigen uptake, processing and presentation capabilities of the dendritic cell in the immune process are enhanced, the initial T cell is effectively activated, the effect function of the T cell is improved, and the killing effect of the T cell on tumor cells is enhanced. The dendritic cell with ATPIF1 knock-down expression has a potential application value in the aspect of preparing immunotherapy drugs for tumors.

The invention discloses a high-efficiency CpG preparation, a preparation method thereof and application. The CpG preparation consists of components including 80-120ml of PBS (phosphate buffer solution) of CpG ODN (oligodeoxynucleotide) with the concentration of 10-45mug/ml, 160-180ml of white oil, 10-14ml of span-80, 6-10ml of tween-80 and 20-40ml of EMULSIGEN. The preparation is quite favorable for strengthening antigen uptake ability of antigen presenting cells, promotes formation of Th1 type immune response, can reduce the application amount of vaccine, improves the service effect of the vaccine, and is higher in stability and more convenient to be stored.

The invention discloses application of 2-(2-difluoromethyl benzimidazole-1-yl)-4,6-dimorpholinyl-1,3,5-triazine (ZSTK474 for short) to preparation of a medicine for treating autoimmune and inflammatory diseases. Experimental results prove that the ZSTK474 can inhibit the differentiation of human immune dendritic cells, the maturity of the lipopolysaccharide (LPS) activated human immune dendritic cells, the antigen uptake capacity of immature dendritic cells, the antigen presenting capacity of mature dendritic cells and T cell proliferation reaction stimulated by the dendritic cells, and particularly can reduce the morbidity degree of mouse experimental autoimmune encephalomyelitis, so the ZSTK474 is expected to become a medicine for treating autoimmune and inflammatory diseases such as multiple sclerosis, acute disseminated encephalomyelitis and the like clinically.

The invention provides an adjuvant for a desensitization vaccine; the adjuvant is prepared from components with immune tolerance; the components with immune tolerance are anti-inflammatory compounds.The invention also provides the novel desensitization vaccine using the anti-inflammatory compounds as the adjuvant. The anti-inflammatory compounds are used as the adjuvant and are co-injected with an allergen, so that inflammation of allergy vaccines is prevented at the injection site; the anti-inflammatory compounds have an effect of inhibiting the maturation of antigen-presenting cells; the anti-inflammatory compounds directly act on the antigen-presenting cells so as to inhibit the antigen-presenting cells from becoming mature cells during antigen uptake and presentation; the anti-inflammatory compounds realizes long-acting treatment of allergies by rapidly inducing the production of Treg cells. The desensitization vaccine provided by the invention can realize rapid, long-acting and effective treatment on the allergies from the view of sensitization mechanism.

Provided is a pharmaceutical composition for preventing or treating cancer, and more particularly, a pharmaceutical composition for preventing or treating cancer, including dendritic cells with a knock-down Dab2 gene. The composition includes a dendritic cell in which a Dab2 gene is knocked down or knocked out or activity of a Dab2 protein is suppressed as an active ingredient, and thus is expected to be useful as a pharmaceutical composition to prevent, improve or treat cancer as a result of having improved antigen uptake, a migration ability of a cell to a lymph node, and expression of inflammatory cytokines, and activating antigen-specific cytotoxic T cell lymphocyte (CTL) and related T cells that can attack cancer cells, and therefore is expected to be used as the pharmaceutical composition for preventing, improving or treating cancer.