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DCS vaccine based on co-encapsulated antigen and dual immune agonist phospholipid hybrid polymer vesicles and its preparation method and application

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

Active Publication Date: 2021-01-05
INST OF BIOMEDICAL ENG CHINESE ACAD OF MEDICAL SCI
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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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 co-encapsulated antigen and dual immune agonist phospholipid hybrid polymer vesicles and its preparation method and application
  • DCS vaccine based on co-encapsulated antigen and dual immune agonist phospholipid hybrid polymer vesicles and its preparation method and application
  • DCS vaccine based on co-encapsulated antigen and dual immune agonist phospholipid hybrid polymer vesicles and its preparation method and application

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preparation example Construction

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

[0036] S1: Dissolve the amphiphilic triblock copolymer PCL-b-PEG-b-PCL and the immune agonist in an organic solvent; then under ice bath conditions, use a 3mm probe with a power of 25% (16W) Ultrasonic cell disruptor was sonicated for 5 minutes, and the antigen solution was dropped during the ultrasonic process to obtain the primary emulsion;

[0037] Among them, the mass ratio of the amphiphilic triblock copolymer PCL-b-PEG-b-PCL and the immune agonist is 20 mg: 2 mg; the molecular weight of the amphiphilic triblock copolymer PCL-b-PEG-b-PCL 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 agonist is one or more of ...

Embodiment 1

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

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

[0051] S2: Under the condition of magnetic stirring at 200 rpm, drop the primary emulsion into 10 mL of swollen polyvinyl alcohol (PVA) solution with a mass fraction of 2% for 2 min, and then wash with 1 mL of deionized water. The washed mixture was immediately sonicated for 10 min with an ultrasonic cell disrupter with a 5 mm probe and a power adjusted to 30% (22 W) under ice bath conditions to obtain a seco...

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 that co-encapsulate antigens and dual immune agonists, and a preparation method and application thereof. 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 (APCs) in the human body. As the initiator of the body's immune response, DCs express MHC I and MHC class II antigenic peptides on their surface, which activate 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 kind of functional dendritic cells carrying antigenic information, which has become a research hotspot in the field of tumor biotherapy. cells that enable T cells to kill tumor cells. DCs can be u...

Claims

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Application Information

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Patent Type & Authority Patents(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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