CCR7 Mediated Mimetic Dendritic Cell Vaccine Homing in Lymph Node for Head and Neck Squamous Cell Carcinoma Therapy.
CCR7 Mediated Mimetic Dendritic Cell Vaccine Homing in Lymph Node for Head and Neck Squamous Cell Carcinoma Therapy.
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DOI：
10.1002/advs.202207017
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发表时间：
2023-06
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影响因子：
--
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中科院分区：
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免疫治疗是头颈部鳞状细胞癌(HNSCC)最有前景的治疗策略之一。树突状细胞(DC)疫苗作为免疫治疗的先驱，已经显示出启动免疫应答的能力，但由于免疫原性不足和低的淋巴结靶向效率，导致临床试验中的治疗效果未经证实。在这里，通过融合肿瘤来源的外切体(TeX)和树突状细胞膜囊泡(DCMV)，开发了一种杂合纳米疫苗(Hy-M-Exo)。该杂合纳米疫苗继承了DCMV的淋巴归巢关键蛋白CCR7，并显示了增强的LN靶向效率。同时，杂合纳米疫苗激活的抗原提呈细胞(APC)中保留的肿瘤抗原和内源性危险信号可引起强烈的T细胞反应。此外，纳米疫苗Hy-M-Exo在HNSCC小鼠模型中显示出良好的治疗效果。这些结果表明，Hy-M-Exo作为一种可行的抗肿瘤免疫治疗策略具有较高的临床价值。将免疫原性肿瘤来源的外切体(TeX)与CCR7保留的树突状细胞膜囊泡(DCMV)杂交，并在MPLA的佐剂下，制备了一种新型的纳米疫苗(Hy-M-Exo)，该疫苗可通过CCR7-CCL21途径靶向淋巴结。HY-M-Exo可诱导肿瘤特异性T细胞渗入肿瘤部位，改变肿瘤微环境，导致肿瘤消退。
Immunotherapy has been recognized as one of the most promising treatment strategies for head and neck squamous cell carcinoma (HNSCC). As a pioneering trend of immunotherapy, dendritic cell (DC) vaccines have displayed the ability to prime an immune response, while the insufficient immunogenicity and low lymph node (LN) targeting efficiency, resulted in an unsubstantiated therapeutic efficacy in clinical trials. Herein, a hybrid nanovaccine (Hy‐M‐Exo) is developed via fusing tumor‐derived exosome (TEX) and dendritic cell membrane vesicle (DCMV). The hybrid nanovaccine inherited the key protein for lymphatic homing, CCR7, from DCMV and demonstrated an enhanced efficiency of LN targeting. Meanwhile, the reserved tumor antigens and endogenous danger signals in the hybrid nanovaccine activated antigen presenting cells (APCs) elicited a robust T‐cell response. Moreover, the nanovaccine Hy‐M‐Exo displayed good therapeutic efficacy in a mouse model of HNSCC. These results indicated that Hy‐M‐Exo is of high clinical value to serve as a feasible strategy for antitumor immunotherapy. Hybridize immunogenic tumor derived exosome (TEX) with CCR7 retained dendritic cell membrane vesicle (DCMV), and adjuvanted by MPLA, to develop a novel nanovaccine (Hy‐M‐Exo), which can target in lymph nodes via the CCR7‐CCL21 way. Hy‐M‐Exo elicits robust tumor‐specific T cells infiltrated in the tumor site, alters the tumor microenvironment, and leads to tumor regression.
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DOI：
10.1126/science.aau6977
发表时间：
2020-02-07
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Kalluri R;LeBleu VS
通讯作者：
LeBleu VS
影响因子：
16
作者：
通讯作者：
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可生物降解的纳米颗粒的临界尺寸极限，用于增强淋巴结运输和副型穿透性。
影响因子：
9.9
作者：
Howard GP;Verma G;Ke X;Thayer WM;Hamerly T;Baxter VK;Lee JE;Dinglasan RR;Mao HQ
通讯作者：
Mao HQ
影响因子：
38.3
作者：
通讯作者：
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影响因子：
5.8
作者：
Chaput, N;Taïeb, J;Zitvogel, L
通讯作者：
Zitvogel, L