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Application of ligand-mediated dendritic cell targeting Texosomes bionic body as tumor vaccine

A technology of dendritic cells and tumor vaccines, which can be used in anti-tumor drugs, pharmaceutical formulations, liposome delivery, etc., can solve the problems of complex glycolipid extraction process and lack of wide applicability, and achieve the reduction of autoimmune reactions, Sustained anti-tumor effect, high purity effect

Active Publication Date: 2015-09-16
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 ligand-mediated dendritic cell targeting Texosomes bionic body as tumor vaccine
  • Application of ligand-mediated dendritic cell targeting Texosomes bionic body as tumor vaccine
  • Application of ligand-mediated dendritic cell targeting Texosomes bionic body as tumor vaccine

Examples

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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 medical technical field and discloses a method for preparing a ligand-mediated dendritic cell targeting nanometer agent serving as a tumor vaccine carrier. According to the method, tumor antigen peptide or a compound formed by tumor antigen peptide and heat shock protein is entrapped in the ligand-modified nanometer agent, the ligand is an antibody capable of being specifically bound with a dendritic cell surface receptor, so that a dendritic cell is specifically targeted, antigenic information is presented onto the surface of the cell through ingestion, processing and treatment of the nanometer agent by means of the dendritic cell, and then recognition of tumor antigen information is achieved by specific cytotoxic T lymphocyte, active immunity of an organism is achieved, tumor cells are killed, and tumor is treated. According to the nanometer agent tumor vaccine preparing method, design is reasonable, preparation is easy, and application prospect is broad.

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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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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