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CN-121975735-A - Extracellular vesicle for inducing monocyte differentiation and preparation method and application thereof

CN121975735ACN 121975735 ACN121975735 ACN 121975735ACN-121975735-A

Abstract

The invention discloses an extracellular vesicle for inducing monocyte differentiation and a preparation method and application thereof, and relates to the technical field of biological medicines. The invention specifically discloses application of extracellular vesicles separated from M1 type macrophages in preparing monocyte-derived macrophages for non-disease diagnosis and treatment, preparing products for preparing monocyte-derived macrophages or preparing medicaments for treating tumors. Extracellular vesicles isolated from M1 type macrophages can induce monocytes to differentiate into antitumor macrophages through TNF-alpha mediated pathways, have excellent blood brain barrier penetration capacity, can effectively reduce tumor volume and prolong survival time, are used for treating tumors such as glioma and the like, and have no off-target toxicity.

Inventors

  • YU CHEN
  • Rao lang
  • PAN YUANWEI
  • LIU XUAN
  • Meng Qianfang

Assignees

  • 深圳湾实验室

Dates

Publication Date
20260505
Application Date
20260130

Claims (10)

  1. 1. Use of extracellular vesicles in any one of A1) to A3): a1 Preparation of monocyte-derived macrophages for non-disease diagnostic therapeutic use; a2 Preparing a product for preparing monocyte-derived macrophages; a3 Preparing a medicament for treating tumors.
  2. 2. The use according to claim 1, wherein the extracellular vesicles are isolated from M1 type macrophages, preferably the extracellular vesicles promote the differentiation of monocytes into macrophages with high expression of anti-tumor markers, preferably the extracellular vesicles inhibit the differentiation of monocytes into macrophages with high expression of pro-tumor markers.
  3. 3. The use of claim 2, wherein the anti-tumor marker comprises at least one of CD80, CD86, TNF- α, iNOS, IL-6, and/or the pro-tumor marker comprises at least one of CD206, mrc1, IL-10.
  4. 4. The use of claim 1, wherein the extracellular vesicles are loaded with at least one of an immune checkpoint inhibitor, a tumor targeting substance, an active pharmaceutical ingredient, optionally the immune checkpoint inhibitor comprises at least one of a CD 47-sirpa signaling axis inhibitor, a PD-1 inhibitor, a PD-L1 inhibitor, a CTLA-4 inhibitor, optionally the tumor targeting substance comprises at least one of a chimeric antigen receptor, an antibody and/or an active fragment thereof that targets a tumor antigen, optionally the tumor antigen comprises at least one of a Wilms tumor protein, a human epidermal growth factor receptor-2, an interleukin-13 receptor subunit a2, EGFRvIII.
  5. 5. The use according to claim 1, wherein the tumor comprises at least one of a solid tumor, a non-solid tumor, preferably the solid tumor comprises at least one of glioma, colon cancer, stomach cancer, liver cancer, bladder cancer, breast cancer, cervical cancer, prostate cancer, melanoma, pancreatic cancer, nasopharyngeal cancer, lung cancer.
  6. 6. A method of preparing a monocyte-derived macrophage comprising the step of contacting a monocyte with an extracellular vesicle as claimed in any one of claims 1 to 5.
  7. 7. The method of claim 6, wherein the extracellular vesicles have an action concentration of 10 μg/mL to 100 μg/mL and/or the extracellular vesicles have an action time of 6h to 48 h.
  8. 8. A macrophage cell, wherein said macrophage cell is differentiated from a monocyte cell.
  9. 9. The macrophage of claim 8, wherein said macrophage comprises an anti-tumor macrophage; Optionally, the monocytes comprise at least one of circulating monocytes, tissue resident monocytes; optionally, the macrophages are derived from M1 type macrophage derived extracellular vesicles that induce monocyte differentiation.
  10. 10. A medicament comprising an extracellular vesicle as claimed in any one of claims 1 to 5.

Description

Extracellular vesicle for inducing monocyte differentiation and preparation method and application thereof Technical Field The invention relates to the technical field of biological medicine, in particular to an extracellular vesicle for inducing monocyte differentiation, and a preparation method and application thereof. Background Gliomas are the most common and invasive primary brain tumors, whose prognosis is still poor despite advances in surgery, radiation and chemotherapy. Immunotherapy is a promising cancer treatment option. However, the benefit of immunotherapy on gliomas is still poor due to the unique brain immune characteristics and immunosuppressive Tumor Microenvironment (TME). One key limitation is poor infiltration and impaired function of T cells, which continue to decrease in both the early and late stages of glioma progression, which renders T cell immunotherapy against gliomas essentially ineffective. The infiltration of monocytes into TME is very pronounced compared to the presence of limited T cells and increases significantly with tumor progression. Circulating monocytes are recruited into the brain in response to inflammatory signals and differentiate into monocyte-derived macrophages (MDMs). However, these MDMs exhibit predominantly immunosuppressive tumor-promoting phenotypes, helping tumor immune evasion by inhibiting antigen presentation and T cell proliferation, thereby promoting immunosuppressive TMEs. Monocytes retain great plasticity and can be reprogrammed to antitumor effect function under appropriate stimulation. Cytokine-based therapies, such as granulocyte-macrophage colony stimulating factor (GM-CSF), can effectively polarize monocytes to antitumor macrophages, but their clinical use in gliomas is limited by poor Blood Brain Barrier (BBB) penetration and systemic inflammatory side effects. mRNA delivery systems provide better persistence in monocyte programming, but their efficacy in gliomas is still limited by the inefficiency of intracranial delivery and potential off-target immune activation. Thus, there is a need for a method of reprogramming monocyte differentiation during glioma progression. Disclosure of Invention The present invention aims to solve at least one of the technical problems existing in the prior art. To this end, the invention proposes the use of extracellular vesicles isolated from M1 type macrophages. The invention also provides a method for preparing monocyte-derived macrophages. The invention also provides a medicament comprising the extracellular vesicles. Use of an extracellular vesicle according to an embodiment of the first aspect of the present invention in any one of A1) to A3): a1 Preparation of monocyte-derived macrophages for non-disease diagnostic therapeutic use; a2 Preparing a product for preparing monocyte-derived macrophages; a3 Preparing a medicament for treating tumors. The application according to the embodiment of the invention has at least the following beneficial effects: Extracellular vesicles isolated from M1-type macrophages are capable of inducing differentiation of monocytes into antitumor macrophages through TNF- α mediated pathways. The tumor-mediated micro-environment-mediated tumor has excellent blood-brain barrier penetrating capability, destroys an immune escape mechanism and activates an innate immune function of phagocytes, can mediate the change of a tumor micro-environment by utilizing a self cell renewal system of an organism as a sustainable drug delivery platform, effectively reduces the tumor volume, prolongs the survival period, is used for treating tumors such as glioma and the like, and does not observe off-target toxicity. This opens up a new path for accurate monocyte engineering, and its application is not limited to the field of cancer, but can be extended to any disease where prognosis is determined by immune cell behavior. According to some embodiments of the invention, the extracellular vesicles are isolated from M1 type macrophages. According to some embodiments of the invention, the product is selected from the group consisting of a reagent, a kit, a medicament, or a culture medium. According to some embodiments of the invention, the macrophages are differentiated from monocytes. The mononuclear cells include mononuclear cells of at least one of bone marrow origin, tumor microenvironment origin, and peripheral blood origin. According to some embodiments of the invention, the extracellular vesicles promote differentiation of monocytes into macrophages with high expression of anti-tumor markers. According to some embodiments of the invention, the anti-tumor marker comprises at least one of CD80, CD86, TNF- α, iNOS, IL-6. According to some embodiments of the invention, the extracellular vesicles inhibit the differentiation of monocytes into macrophages with high expression of a tumor promoting marker. According to some embodiments of the invention, the tumor promoting marker comprises at least one o