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CCR7 介导的模拟树突状细胞疫苗归巢于颈部淋巴结用于头颈部鳞状细胞癌治疗。

CCR7 Mediated Mimetic Dendritic Cell Vaccine Homing in Lymph Node for Head and Neck Squamous Cell Carcinoma Therapy.

机构信息

Hospital of Stomatology, Sun Yat-sen University, Guangzhou, 510030, P. R. China.

Guangdong Provincial Key Laboratory of Stomatology, Guangzhou, 510030, P. R. China.

出版信息

Adv Sci (Weinh). 2023 Jun;10(17):e2207017. doi: 10.1002/advs.202207017. Epub 2023 Apr 24.

DOI:10.1002/advs.202207017
PMID:37092579
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10265089/
Abstract

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.

摘要

免疫疗法已被认为是治疗头颈部鳞状细胞癌（HNSCC）最有前途的治疗策略之一。作为免疫疗法的一种开创性趋势，树突状细胞（DC）疫苗显示出能够引发免疫反应的能力，但其免疫原性不足和低淋巴结（LN）靶向效率导致临床试验中的治疗效果不佳。在此，通过融合肿瘤衍生的外泌体（TEX）和树突状细胞膜囊泡（DCMV），开发了一种混合纳米疫苗（Hy-M-Exo）。该混合纳米疫苗从 DCMV 继承了用于淋巴归巢的关键蛋白 CCR7，从而提高了 LN 靶向效率。同时，混合纳米疫苗中保留的肿瘤抗原和内源性危险信号激活了抗原呈递细胞（APC），引发了强烈的 T 细胞反应。此外，纳米疫苗 Hy-M-Exo 在 HNSCC 小鼠模型中表现出良好的治疗效果。这些结果表明，Hy-M-Exo 具有很高的临床价值，可作为一种可行的抗肿瘤免疫治疗策略。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/91c8/10265089/be9bb62adb8e/ADVS-10-2207017-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/91c8/10265089/742c4209eff6/ADVS-10-2207017-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/91c8/10265089/496b8e4ffc73/ADVS-10-2207017-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/91c8/10265089/c8d0540404d4/ADVS-10-2207017-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/91c8/10265089/ed11a55a0957/ADVS-10-2207017-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/91c8/10265089/cf761b6815eb/ADVS-10-2207017-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/91c8/10265089/be9bb62adb8e/ADVS-10-2207017-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/91c8/10265089/742c4209eff6/ADVS-10-2207017-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/91c8/10265089/496b8e4ffc73/ADVS-10-2207017-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/91c8/10265089/c8d0540404d4/ADVS-10-2207017-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/91c8/10265089/ed11a55a0957/ADVS-10-2207017-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/91c8/10265089/cf761b6815eb/ADVS-10-2207017-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/91c8/10265089/be9bb62adb8e/ADVS-10-2207017-g004.jpg

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