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Fusion cell membrane nano-vesicle for tumor immunotherapy as well as preparation method and application of fusion cell membrane nano-vesicle

A nanovesicle and immunotherapy technology, applied in the field of biomedicine, can solve problems such as poor treatment effect, and achieve the effect of improving the treatment effect and improving the treatment effect.

Pending Publication Date: 2021-12-10
SHENZHEN BAY LAB
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

However, for tumor cells that express both PD-L1 and CD47, this method only blocks the PD-L1 / PD-1 signaling pathway, and its therapeutic effect is not good.

Method used

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  • Fusion cell membrane nano-vesicle for tumor immunotherapy as well as preparation method and application of fusion cell membrane nano-vesicle
  • Fusion cell membrane nano-vesicle for tumor immunotherapy as well as preparation method and application of fusion cell membrane nano-vesicle
  • Fusion cell membrane nano-vesicle for tumor immunotherapy as well as preparation method and application of fusion cell membrane nano-vesicle

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preparation example Construction

[0034] According to a typical embodiment of the present invention, a method for preparing the above fused cell membrane nanovesicles is provided. The preparation method includes the following steps: selecting two or more immune checkpoints of tumor cells, and genetically engineering the cells to obtain cells that overexpress the receptors corresponding to the immune checkpoints, wherein the overexpression of the immune checkpoints corresponds to There are two or more kinds of receptor cells, and each cell overexpressing the corresponding receptor of the immune checkpoint overexpresses one or more receptors corresponding to the immune checkpoint; respectively prepare the cells derived from the overexpression of the immune checkpoint Single cell membrane vesicle components of the corresponding recipient cells; and fusion of two or more single cell membrane vesicle components to obtain fusion cell membrane nanovesicles.

[0035] The preparation method of this method does not requ...

Embodiment

[0052] Materials: Chemical reagents were purchased from Sigma Aldrich unless otherwise stated. Both anti-PD-L1 and anti-CD47 monoclonal antibodies were derived from Bio-X cells.

[0053] Cell lines: The mouse cell lines of B16F10 melanoma (B16F10 cells), 4T1 breast cancer (4T1 cells) and RAW 264.7 macrophages were all obtained from the American Type Culture Collection (ATCC) and cultured under the guidance provided by ATCC.

[0054] Mice: Female BALB / c mice or C57BL / 6 mice (6-10 weeks) were purchased from Beijing Vital River Laboratory Animal Technology Co., Ltd.

[0055] The specific operations and results are as follows:

[0056] First, the construction and identification of genetically engineered cells. SIRPα variants and PD-1 were overexpressed by lentivirus on 4T1 mouse mammary tumor and B16F10 mouse melanoma cells, respectively. Expression of SIRPα variants and PD-1 on corresponding cells by immunofluorescence imaging and flow cytometry ( figure 1 a and b) in to conf...

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Abstract

The invention discloses a fusion cell membrane nano-vesicle for tumor immunotherapy as well as a preparation method and application of the fusion cell membrane nano-vesicle. The fusion cell membrane nano-vesicle is formed by fusing two or more cell membrane vesicles from cells of different sources, and the cell membrane vesicles from the cells of different sources overexpress receptors corresponding to different immune checkpoints. The fusion cell membrane vesicle does not need complex design and preparation, and does not bring immunotoxicity; compared with the cell membrane vesicles with a single target marker, the fusion cell membrane nano-vesicle has the advantages that the treatment effect is improved, and compared with cocktail therapy in which the cell membrane vesicles with different target markers are simply mixed and used, the fusion cell membrane nano-vesicle has the advantages that the treatment effect is also improved; besides, a single cell membrane vesicle component in the fusion cell membrane vesicle can be customized independently, so that the structure has high degree of freedom, and various different tumor cells can be selectively targeted; and due to homologous targeting and immune antigens of tumor cell membranes, the treatment effect on various tumors can be improved at the same time.

Description

technical field [0001] The invention relates to the technical field of biomedicine, in particular to a fused cell membrane nanovesicle for tumor immunotherapy, its preparation method and application. Background technique [0002] Immune checkpoint blockade therapy (ICB therapy) belongs to tumor immunotherapy. Among them, immune blocking points include adaptive and innate immune blocking points, such as PD-L1 and CD47. As an adaptive immune blocking point, PD-L1 can inhibit the activity of anti-tumor T cells and reduce the anti-tumor adaptive immune response through the PD-1 receptor. Therefore, the PD-L1 / PD-1 signaling pathway Disruption of T cells restores the immune response against tumor T cells. As an innate immune blocking point, CD47 can reduce the phagocytosis of macrophages by interacting with its receptor (signal regulatory protein SIRPα). Therefore, blocking CD47 and SIRPα signaling pathways can also inhibit tumor growth. [0003] Since both PD-L1 and CD47 can ...

Claims

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Application Information

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IPC IPC(8): A61K47/46A61K9/127A61K45/00A61P35/00B82Y5/00B82Y40/00
CPCA61K47/46A61K9/127A61K45/00A61P35/00B82Y5/00B82Y40/00
Inventor 饶浪
Owner SHENZHEN BAY LAB
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