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DCs vaccine based on phospholipid hybrid polymersome jointly encapsulating antigen and dual immunoagonists and preparation method and application thereof

An agonist and polymer technology, applied in the field of biomedical engineering, can solve the problems of incomplete maturity, lack of cross-presentation of DCs, inability of DCs to effectively carry antigens and activators, etc., to enhance immune response and maximize targeting effect , The effect of optimizing the immune effect

Active Publication Date: 2018-12-07
INST OF BIOMEDICAL ENG CHINESE ACAD OF MEDICAL SCI
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, the effective immune response of DCs vaccines is relatively low at present. The main reasons are: (1) The current method cannot make DCs effectively carry antigens and activators, resulting in the lack of cross-presentation of DCs and the inability to fully mature; Due to the low migration response of the factor, the localization ability of the DCs vaccine in vivo is limited, and only 5% or less migrate to the lymph nodes

Method used

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  • DCs vaccine based on phospholipid hybrid polymersome jointly encapsulating antigen and dual immunoagonists and preparation method and application thereof
  • DCs vaccine based on phospholipid hybrid polymersome jointly encapsulating antigen and dual immunoagonists and preparation method and application thereof
  • DCs vaccine based on phospholipid hybrid polymersome jointly encapsulating antigen and dual immunoagonists and preparation method and application thereof

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preparation example Construction

[0035] The present invention provides a DCs vaccine based on phospholipid hybrid polymer vesicles co-encapsulating antigens and dual immune agonists. The preparation method comprises steps:

[0036] S1: Dissolve the amphiphilic triblock copolymer PCL-b-PEG-b-PCL and the immune stimulant in an organic solvent; Ultrasonic cell disruptor was used to sonicate for 5 minutes, and the antigen solution was dropped into the sonication process to obtain the primary emulsion;

[0037] Wherein, the mass ratio of the amphiphilic triblock copolymer PCL-b-PEG-b-PCL and the immune stimulant is 20mg:2mg; the molecular weight of the amphiphilic triblock copolymer PCL-b-PEG-b-PCL It is 10000-24000, preferably 16000, wherein the mass percentage of PEG hydrophilic segment is greater than 45%; the amphiphilic triblock copolymer PCL-b-PEG-b-PCL is preferably PCL 4000 -PEG 8000 -PCL 4000 The immune stimulant is one or more of TLR4, TLR7 / 8, TLR1, TLR2, TLR5, TLR6, TLR3 and TLR9; preferably, the TLR...

Embodiment 1

[0049] This example provides a DCs vaccine based on phospholipid hybrid polymer vesicles co-encapsulating antigens and dual immune agonists. The preparation method includes steps:

[0050] S1: 20 mg amphiphilic triblock copolymer PCL 4000 -PEG 8000 -PCL 4000 and 2mg of TLR7 / 8 agonist IMQ were dissolved in 1mL of dichloromethane; after fully dissolving, in an ice bath, ultrasonicated for 5min with a 3mm probe and an ultrasonic cell disruptor with power adjusted to 25% (16W). Add 200 μL of 10 mg / mL OVA antigen solution to obtain a primary emulsion.

[0051] S2: Under the condition of magnetic stirring at 200rpm, drop the primary emulsion into 10mL of swollen polyvinyl alcohol (PVA) solution with a mass fraction of 2%, and the dropping time is 2min, then wash it with 1mL deionized water. Immediately, the cleaned mixture was ultrasonicated for 10 min with a 5mm probe and an ultrasonic cell disruptor with power adjusted to 30% (22W) in an ice bath to obtain a secondary emulsion....

Embodiment 2- Embodiment 11

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Abstract

The invention relates to a DCs vaccine based on phospholipid hybrid polymersome jointly encapsulating an antigen and dual immunoagonists, a preparation method and application thereof. The phospholipidhybrid polymersome which can jointly load a model antigen OVA and two types of TLR agonists (TLR7 / 8 and TLR4) is used for stimulation in vitro of the DCs so as to realize the effective phagocytosis of DCs cells. The rapid and long-term immunostimulatory effect on the DCs is achieved by the internal and external co-loading of the OVA antigen. The synergistic effect of the two types of TLR agonistssignificantly enhances the immune response after antigen stimulation; the phospholipid hybrid polymersome which jointly encapsulates the antigen and the dual immunoagonists can effectively promote the activation and maturation of the DCs, increases the level of cross-presentation, promotes the migration of the DC vaccine to secondary lymphoid organs, and produces a strong specific cytotoxic T lymphocytes (CTLs) killing effect, thereby effectively killing tumor cells and realizing the immunotherapy of the DCs vaccine on tumors.

Description

technical field [0001] The invention relates to the technical field of biomedical engineering, in particular to a DCs vaccine based on phospholipid hybrid polymer vesicles co-encapsulating antigens and dual immune agonists, as well as its preparation method and application. Background technique [0002] Dendritic cells (DCs) exist in human peripheral blood, skin, thymus and lymphoid organs, and are the most powerful professional antigen-presenting cells (Antigen-presenting cells, APCs) in the human body. As the initiator of the body's immune response, DCs express MHC class I and MHC class II antigen peptides on their surface, through activation of CD4 + Th and CD8 + CTL cells control the level of immune response and become a key link in anti-tumor immunotherapy. [0003] Dendritic cell vaccine (DCs vaccine) is a type of functional dendritic cells carrying antigen information, which has become a research hotspot in the field of tumor biotherapy today. Its advantage is that ...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K9/127A61K47/24A61K47/34A61K39/00A61P35/00
CPCA61K9/1273A61K39/0011A61K47/24A61K47/34A61P35/00
Inventor 张琳华朱敦皖胡春艳樊帆郭勍
Owner INST OF BIOMEDICAL ENG CHINESE ACAD OF MEDICAL SCI
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