Bone Marrow Dendritic Cells Derived Microvesicles for Combinational Immunochemotherapy against Tumor,Advanced Functional Materials

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Bone Marrow Dendritic Cells Derived Microvesicles for Combinational Immunochemotherapy against Tumor
Advanced Functional Materials ( IF 18.5 ) Pub Date : 2017-09-13 , DOI: 10.1002/adfm.201703191
Tingting Wu ₁ , Yan Qi ₁ , Dan Zhang ₁ , Qingle Song ₁ , Conglian Yang ₁ , Xiaomeng Hu ₁ , Yuling Bao ₁ , Yongdan Zhao ₁ , Zhiping Zhang _{1,

2,

3}

Affiliation

Various types of cell can change the cytoskeleton and shed microvesicles (MVs) with biomimic properties as parent cells in response to stimuli. To take use of the drug package capability of MVs and the potent antigen presentation property of dendritic cells (DCs), DC‐derived antigenic MVs are constructed by priming DCs with tumor‐derived MVs and then encapsulating a chemotherapeutic drug during MVs shedding. This kind of MVs exhibit significant inhibition on melanoma tumor growth and metastasis. The MV‐encapsulated chemotherapeutics can induce direct cytotoxicity and immunogenic cell death in tumor cells. Moreover, a robust antitumor immunity is induced in both, the tumor‐draining lymph node and the tumor microenvironment as the infiltration and activation of T lymphocytes increases. This kind of MVs is further explored in a hepatic ascites model with remarkable prolonged overall survival of mice. More importantly, the MVs can extend the survival of 60% mice more than 150 d without ascites even after rechallenging the tumor twice. This study demonstrates that antigenic MVs with chemotherapeutics possess great potential in cancer immunochemotherapy.

中文翻译：

骨髓树突状细胞衍生的微囊泡，用于肿瘤的联合免疫化学疗法。

各种类型的细胞都可以改变其母体具有仿生特性的细胞骨架和脱落的微囊泡（MVs），以响应刺激。为了利用MV的药物包装能力和树突状细胞（DC）的有效抗原呈递特性，可通过用肿瘤衍生的MV引发DC，然后在MV脱落过程中封装化疗药物来构建DC衍生的抗原MV。这类MV对黑素瘤肿瘤的生长和转移具有明显的抑制作用。MV封装的化学疗法可在肿瘤细胞中诱导直接的细胞毒性和免疫原性细胞死亡。此外，随着T淋巴细胞的浸润和活化增加，引流淋巴结和肿瘤微环境均诱导出强大的抗肿瘤免疫力。在具有明显延长的小鼠整体存活期的肝腹水模型中进一步探索这种MV。更重要的是，即使在两次再次挑战肿瘤后，MV仍可将60％的小鼠的存活期延长至150天以上而无腹水。这项研究表明，具有化学治疗作用的抗原性MVs在癌症免疫化学疗法中具有巨大的潜力。

更新日期：2017-09-13

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