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Dual-targeted nanomedicine for customized T-cell epitope vaccine, preparation method and application thereof

An epitope vaccine and dual-targeting technology, applied in nanotechnology, nanomedicine, and nanotechnology for materials and surface science, can solve problems such as uncontrollable drug release, reduce degradation and loss, and reduce toxic and side effects Effect

Active Publication Date: 2021-05-07
JIANGSU PROVINCE HOSPITAL THE FIRST AFFILIATED HOSPITAL WITH NANJING MEDICAL UNIV +2
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Traditional drug delivery systems are often accompanied by non-specific biodistribution and uncontrollable drug release

Method used

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  • Dual-targeted nanomedicine for customized T-cell epitope vaccine, preparation method and application thereof
  • Dual-targeted nanomedicine for customized T-cell epitope vaccine, preparation method and application thereof
  • Dual-targeted nanomedicine for customized T-cell epitope vaccine, preparation method and application thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0051] (1) Preparation of targeted killer polymer

[0052] 1) Customized specific targeting polymer: select the pathogenic CD8+ T cell-specific antigen peptide IGRP206-214 of Tcra TcrbNY8.3 mouse, and synthesize the corresponding biotinylated MHC Class I polymer with mouse H-2kd Body (Proimmune, UK).

[0053] 2) Select the streptomycin / saporin complex (Streptavidin-ZAP), mix it with the customized biotin-labeled pMHC pentamer in an equimolar ratio, mix well and incubate at room temperature for 15 minutes, then place the mixture in- Store at 20°C, shake gently before use, and dilute as needed.

[0054] (2) Preparation of targeted nano-drugs

[0055] 1) Dissolve PLGA (300 mg) in DCM (20 mL), emulsify the targeted killer polymer solution into the PLGA solution using a probe sonicator, and set the amplitude at 40% for 100 s in an ice bath.

[0056] 2) Pour the W / O colostrum into the PVA solution (3%), and homogenize it in an ice bath at 6000 rpm for 30 minutes using a high-spee...

Embodiment 2

[0064] (1) Preparation of targeted killer polymer

[0065] 1) Customized specific targeting polymers: clinically, different patients screen out the pathogenic CD8+ T cells with dominant expression in their body according to their peripheral blood, and customize the individual according to the epitope polypeptide type of the pathogenic T cells MHC Class I polymer (pMHC multimer) (Proimmune, UK) marked with the polypeptide-Tag sequence.

[0066] 2) Mix the pMHC multimer linked with the Tag sequence and the saponin protein linked with the anti-Tag sequence in an equimolar ratio, mix thoroughly and incubate at room temperature for 15 minutes, then store the mixture at -20°C, and gently wash it before use. Shake to dilute as needed.

[0067] (2) Preparation of targeted nano-drugs

[0068] 1) DPPC, DSPC, and DSPE-PEG2K were fully dissolved in chloroform at a molar ratio of 90:5:5, then protein G antibody (Abcam, UK) was added, and mixed well.

[0069] 2) Evaporate in vacuo under ...

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Abstract

The invention belongs to the technical field of nanomedicine, and in particular relates to a novel double-targeting nanomedicine of a customized T cell epitope vaccine, its preparation method and application. The nanomedicine comprises: i) pMHC multimer; ii) saponin protein linked to pMHC multimer; iii) nanocarrier, which encapsulates i) and ii) in it; iv) human pancreas-specific expression Antibodies to cell surface membrane antigens attached to the outside of the nanocarrier. According to the different islet antigen pathogenic T cells in the patient, the nanomedicine can customize the toxic pMHC multimer suitable for different patients' antigenic polypeptides to kill the islet antigen pathogenic T cells, and screen out human pancreas-specific targets The antibody is connected to nanocarriers externally, so that the nanomedicine can be mainly concentrated in the pancreas to increase the efficacy of the drug, reduce the drug concentration and the toxic side effects of large-dose systemic administration, and it is a customized, pancreas and pathogenic T cell double target Nano-drugs for precise immunotherapy.

Description

technical field [0001] The invention belongs to the technical field of nanomedicine, and in particular relates to a dual-target nanomedicine of a customized T cell epitope vaccine, its preparation method and application. Background technique [0002] Type 1 diabetes is an organ-specific autoimmune disease characterized by T cell-mediated destruction of pancreatic β cells. Pancreatic beta cells are the only cells that secrete insulin, which controls blood sugar. The current mainstream treatment of insulin supplementation has changed type 1 diabetes from an acute and fatal disease to a chronic disease, but insulin cannot stop the process of islet autoimmune attack. In the short term, patients will eventually develop brittle diabetes with frequent severe hypoglycemia and huge fluctuations in blood sugar due to the complete loss of islet function. [0003] Islet autoantigen-specific T cells are key to islet β-cell destruction in type 1 diabetes. A triggering event (currently ...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): A61K47/69A61K47/68A61K47/64A61K38/17A61P3/10B82Y5/00B82Y30/00B82Y40/00
CPCA61K38/1774A61K47/64A61K47/6849A61K47/6913A61P3/10B82Y5/00B82Y30/00B82Y40/00
Inventor 许馨予杨涛赵瑞苓杨芳
Owner JIANGSU PROVINCE HOSPITAL THE FIRST AFFILIATED HOSPITAL WITH NANJING MEDICAL UNIV
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