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A CAR T-inspiring platform based on antibody-engineered exosomes from antigen-feeding dendritic cells for precise solid tumor therapy

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机构: [1]Hebei Univ, Coll Chem & Environm Sci, Chem Biol Key Lab Hebei Prov, Key Lab Med Chem & Mol Diag,Minist Educ, Baoding 071002, Peoples R China [2]Southern Med Univ, Affiliated Dongguan Hosp, Dongguan 523059, Peoples R China [3]Guangdong Prov Key Lab Shock & Microcirculat, Guangzhou 510515, Guangdong, Peoples R China [4]Hebei Univ, Coll Pharmaceut Sci, Key Lab Pharmaceut Qual Control Hebei Prov, Baoding 071002, Peoples R China [5]Natl Ctr Nanosci & Technol, CAS Key Lab Biol Effects Nanomat & Nanosafety, Beijing 100190, Peoples R China [6]Hebei Univ, Coll Med Sci, Baoding 071002, Peoples R China [7]Hebei Univ, Affiliated Hosp, Baoding 071000, Peoples R China
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关键词: Engineered-exosome CAR-mimicking CAR T cell therapy Immunotherapy Solid tumor

摘要:
Chimeric antigen receptor T (CAR T) cell therapy has achieved remarkable results treating patients with he-matological malignancies in clinical studies. Although promising, extensive research has also revealed that CAR T therapy is unsatisfactory for the treatment of solid tumors. In addition, the production of CAR T cells is time-consuming and it's hard for storage and transportation. In this work, inspired by the construction of CAR T cell, we developed an antibody-engineered exosomes from antigen-feeding dendritic cells for beyond CAR T therapy of solid tumor by in situ T cells activation and cancer cell targeting. We have confirmed that tumor antigen-stimulated dendritic cell-derived exosomes (tDC-Exo) provided major histocompatibility (MHC)-antigen com-plexes and CD86 co-stimulating molecules, which were the same as CAR of CAR T cell acting as the necessary signals for T cell activation. Furthermore, anti-CD3 and anti-EGFR were then engineered on tDC-Exo to promote the binding of T cell to cancer cells for precise therapy. Our CAR T cell therapy-mimicking system have shown an efficient endogenous T cells activation and their crosslinking with cancer cells for enhanced solid tumor therapy. More interestingly, we found that immune activation significantly up-regulated PD-L1 expression, and thus we confirmed the combination with anti-PD-L1 antibodies further enhanced the efficacy of our CAR T cell therapy-mimicking platform.

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出版当年[2023]版:
大类 | 1 区 医学
小类 | 1 区 工程:生物医学 1 区 材料科学:生物材料
最新[2025]版:
大类 | 1 区 医学
小类 | 1 区 工程:生物医学 1 区 材料科学:生物材料
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出版当年[2022]版:
Q1 ENGINEERING, BIOMEDICAL Q1 MATERIALS SCIENCE, BIOMATERIALS
最新[2023]版:
Q1 ENGINEERING, BIOMEDICAL Q1 MATERIALS SCIENCE, BIOMATERIALS

影响因子: 最新[2023版] 最新五年平均 出版当年[2022版] 出版当年五年平均 出版前一年[2021版] 出版后一年[2023版]

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第一作者机构: [1]Hebei Univ, Coll Chem & Environm Sci, Chem Biol Key Lab Hebei Prov, Key Lab Med Chem & Mol Diag,Minist Educ, Baoding 071002, Peoples R China
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通讯机构: [2]Southern Med Univ, Affiliated Dongguan Hosp, Dongguan 523059, Peoples R China [3]Guangdong Prov Key Lab Shock & Microcirculat, Guangzhou 510515, Guangdong, Peoples R China [*1]College of Chemistry & Environmental Science, Chemical Biology Key Laboratory of Hebei Province, Key Laboratory of MedicinalChemistry and Molecular Diagnosis of the Ministry of Education, Hebei University, Baoding, 071002, China
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