Boron Neutron Capture Therapy‐Derived Extracellular Vesicles via DNA Accumulation Boost Antitumor Dendritic Cell Vaccine Efficacy

Author:

Lv Linwen12,Zhang Junzhe3,Wang Yujiao1,Liang Haojun1,Liu Qiuyang1,Hu Fan1,Li Hao1,Su Wenxi1,Zhang Junhui1,Chen Ranran1,Chen Ziteng1,Wang Zhijie1,Li Jiacheng1,Yan Ruyu1,Yang Mingxin1,Chang Ya‐nan1,Li Juan1,Liang Tianjiao4,Xing Gengmei1,Chen Kui1ORCID

Affiliation:

1. CAS Key Lab for Biomedical Effects of Nanomaterials and Nanosafety Institute of High Energy Physics Chinese Academy of Sciences 19B YuquanLu, Shijingshan District Beijing 100049 China

2. University of Chinese Academy of Sciences Beijing 100049 China

3. State Key Laboratory for Quality Ensurance and Sustainable Use of Dao‐di Herbs Artemisinin Research Center and Institute of Chinese Materia Medica China Academy of Chinese Medical Sciences Beijing 100700 China

4. Guangdong‐Hong Kong‐Macao Joint Laboratory for Neutron Scattering Science and Technology Spallation Neutron Source Science Center Dongguan 523803 China

Abstract

AbstractRadiated tumor cell‐derived extracellular vesicles (RT‐EVs) encapsulate abundant DNA fragments from irradiated tumor cells, in addition to acting as integrators of multiple tumor antigens. Accumulating evidence indicates these DNA fragments from damaged cells are involved in downstream immune responses, but most of them are degraded in cells before incorporation into derived RT‐EVs, thus the low abundance of DNA fragments limits immune responses of RT‐EVs. Here, this study found that different radiations affected fates of DNA fragments in RT‐EVs. Boron neutron capture therapy (BNCT) induced DNA accumulation in RT‐EVs (BEVs) by causing more DNA breaks and DNA oxidation resisting nuclease degradation. This is attributed to the high‐linear energy transfer (LET) properties of alpha particles from the neutron capture reaction of 10B. When being internalized by dendritic cells (DCs), BEVs activated the DNA sensing pathway, resulting in functional enhancements including antigen presentation, migration capacity, and cytokine secretion. After vaccination of the BEVs‐educated DCs (BEV@BMDCs), the effector T cells significantly expanded and infiltrated into tumors, suggesting robust anti‐tumor immune activation. BEV@BMDCs not only effectively inhibited the primary tumor growth and metastasis formation but also elicited long‐term immune memory. In conclusion, a successful DC vaccine is provided as a promising candidate for tumor vaccine.

Funder

National Natural Science Foundation of China

National Basic Research Program of China

Basic and Applied Basic Research Foundation of Guangdong Province

Beijing Nova Program

Publisher

Wiley

同舟云学术

1.学者识别学者识别

2.学术分析学术分析

3.人才评估人才评估

"同舟云学术"是以全球学者为主线,采集、加工和组织学术论文而形成的新型学术文献查询和分析系统,可以对全球学者进行文献检索和人才价值评估。用户可以通过关注某些学科领域的顶尖人物而持续追踪该领域的学科进展和研究前沿。经过近期的数据扩容,当前同舟云学术共收录了国内外主流学术期刊6万余种,收集的期刊论文及会议论文总量共计约1.5亿篇,并以每天添加12000余篇中外论文的速度递增。我们也可以为用户提供个性化、定制化的学者数据。欢迎来电咨询!咨询电话:010-8811{复制后删除}0370

www.globalauthorid.com

TOP

Copyright © 2019-2024 北京同舟云网络信息技术有限公司
京公网安备11010802033243号  京ICP备18003416号-3