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Application of a ligand-mediated dendritic cell-targeted texosome biomimetic as a tumor vaccine

A technology for dendritic cells and tumor vaccines, which is applied in anti-tumor drugs, pharmaceutical formulations, liposome delivery, etc., can solve the problems of complex glycolipid extraction process, lack of wide applicability, etc. Sustained anti-tumor effect, high-purity effect

Active Publication Date: 2018-03-30
SHENYANG PHARMA UNIVERSITY
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

The patented glycolipid extraction process is complicated, and it has strong restrictions on the ligands modified on the surface of the preparation and the surface receptors of dendritic cells, and it does not have wide applicability

Method used

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  • Application of a ligand-mediated dendritic cell-targeted texosome biomimetic as a tumor vaccine
  • Application of a ligand-mediated dendritic cell-targeted texosome biomimetic as a tumor vaccine
  • Application of a ligand-mediated dendritic cell-targeted texosome biomimetic as a tumor vaccine

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0026]Example 1: Preparation of nanoliposomes coupled with DEC205 monoclonal antibody by reverse evaporation method

[0027] Accurately weigh 30.0 mg of phospholipids, 5.0 mg of carbamoyl cholesterol hydrochloride, and 5.0 mg of cholesterol monosuccinate, add 10 ml of dichloromethane to dissolve them, and slowly drop in 100 μg / ml of tumor antigen peptide MAGE-3 at room temperature The solution was used as the water phase, stirred magnetically for 10 minutes to form an emulsion, vortex mixed for 3 minutes, and then evaporated in a water bath at 60°C to remove the organic solvent. After the complete phase inversion into an aqueous liquid, stop the evaporation under reduced pressure, and add the external water phase dropwise and stir for 30 minutes. Fully hydrated, after 5 minutes of ultrasound with the probe in an ice bath, feed materials according to the molar ratio of cholesterol monosuccinate: N-hydroxysuccinimide: carbodiimide hydrochloride 1:1.5:1.5, react for 12 hours, and ...

Embodiment 2

[0028] Example 2: Preparation of DEC205 monoclonal antibody-coupled Texosomes biomimetic body by layer-by-layer assembly method

[0029] (1) Preparation of Texosomes bionic body

[0030] Accurately weigh 15.0 mg of phospholipid and 5.0 mg of polyoxyethylene castor oil, add 10 ml of ether to dissolve them, and slowly drop in the hTERT-HSP70 solution of the complex of general tumor antigen and heat shock protein 70 with a concentration of 100 μg / ml at 25 °C 1ml to prepare the microemulsion phase. Accurately weigh 20.0mg of dioleoylphosphatidylethanolamine DOPE, 5.0mg of DC-Chol and 5.0mg of cholesterol monosuccinate CHS, add 5ml of ether to dissolve them, evaporate under reduced pressure at 30°C to form a film, add 1.5ml of distilled water and ethanol 0.5ml, and hydrated at 50°C to prepare the micellar phase. The two phases were vortex mixed for 5 minutes, the organic solvent was removed by rotary evaporation at 50°C, and the Texosomes bionics were prepared after the probe was...

Embodiment 3

[0034] (1) Preparation of Texosomes bionic body

[0035] Accurately weigh 10.0 mg of phospholipid and 8.0 mg of polyoxyethylene castor oil, add 10 ml of ether to dissolve them, and slowly drop into the hTERT-gp96 solution of the complex of general tumor antigen and heat shock protein gp96 at a concentration of 500 μg / ml at 10 °C 0.5ml to prepare the microemulsion phase. Accurately weigh 20.0mg of dioleoylphosphatidylethanolamine DOPE, 5.0mg of DC-Chol and 5.0mg of cholesterol monosuccinate CHS, add 10ml of ether to dissolve them, evaporate under reduced pressure at 20°C to form a film, add 0.8ml of distilled water and ethanol 0.2ml, and hydrated at 40°C to prepare the micellar phase. The two phases were vortex mixed for 8 minutes, the organic solvent was removed by rotary evaporation at 40°C, and the Texosomes bionics were prepared after the probe was sonicated for 3 minutes in an ice bath.

[0036] (2) Modification of ligands on the surface of Texosomes biomimetic body

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Abstract

The invention belongs to the technical field of medicine, and relates to a method for constructing a ligand-mediated nano-preparation targeting dendritic cells as a tumor vaccine carrier. In the present invention, tumor antigen peptides or complexes formed by tumor antigen peptides and heat shock proteins are encapsulated in ligand-modified nano-preparations, and the ligands are antibodies that can specifically bind to dendritic cell surface receptors, thereby Specifically target dendritic cells, and present antigen information to the cell surface through the uptake, processing and processing of nano-preparations by dendritic cells, and then realize the recognition of tumor antigen information by specific cytotoxic T lymphocytes, Make the body produce active immunity, eliminate tumor cells, and achieve the therapeutic effect on tumors. The preparation method of the nano-preparation tumor vaccine provided by the invention is reasonable in design, simple in preparation and has broad application prospects.

Description

technical field [0001] The invention relates to the technical field of medicine, and relates to the application of a ligand-mediated Texosomes bionic body targeting dendritic cells as a tumor vaccine. Background technique [0002] Tumor formation is the result of immune escape of tumor antigens, and the body's immune tolerance and immunosuppression promote tumor growth and metastasis. How to activate and enhance the inherent immune response of tumor patients to suppress tumors and reduce the possibility of escaping immune surveillance is the main goal of modern tumor therapy. Tumor immunotherapy is to improve the body's immune response to tumor cells by mobilizing the host's natural defense mechanism, enhancing the host's immune defense effect, and reducing the host's immune suppression, thereby killing or inhibiting tumor cells. At present, this treatment method has become the fourth important tumor treatment mode after surgery, chemotherapy, and radiotherapy, and has the ...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): A61K39/00A61K39/39A61K9/127A61K47/24A61K47/18A61K47/14A61P35/00
Inventor 李可欣常莎莎陈大为王中彦
Owner SHENYANG PHARMA UNIVERSITY
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