1. Academic Validation
  2. Boron Neutron Capture Therapy-Derived Extracellular Vesicles via DNA Accumulation Boost Antitumor Dendritic Cell Vaccine Efficacy

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

  • Adv Sci (Weinh). 2024 Jul 17:e2405158. doi: 10.1002/advs.202405158.
Linwen Lv 1 2 Junzhe Zhang 3 Yujiao Wang 1 Haojun Liang 1 Qiuyang Liu 1 Fan Hu 1 Hao Li 1 Wenxi Su 1 Junhui Zhang 1 Ranran Chen 1 Ziteng Chen 1 Zhijie Wang 1 Jiacheng Li 1 Ruyu Yan 1 Mingxin Yang 1 Ya-Nan Chang 1 Juan Li 1 Tianjiao Liang 4 Gengmei Xing 1 Kui Chen 1
Affiliations

Affiliations

  • 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

Radiated 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.

Keywords

DC vaccine; DNA; anti‐tumor immunity; boron neutron capture therapy; radiated tumor cell‐derived extracellular vesicles.

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