Alarmin-painted exosomes elicit persistent antitumor immunity in large established tumors in mice

Bingfeng Zuo, Han Qi, Zhen Lu, Lu Chen, Bo Sun, Rong Yang, Yang Zhang, Zhili Liu, Xianjun Gao, Abin You, Li Wu, Renwei Jing, Qibing Zhou and HaiFang Yin ()
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Bingfeng Zuo: Tianjin Medical University
Han Qi: Tianjin Medical University
Zhen Lu: Tianjin Medical University
Lu Chen: Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy
Bo Sun: Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy
Rong Yang: Huazhong University of Science and Technology
Yang Zhang: Tianjin Medical University
Zhili Liu: Tianjin Medical University
Xianjun Gao: Tianjin Medical University
Abin You: Tianjin Medical University
Li Wu: Tianjin Medical University
Renwei Jing: Tianjin Medical University
Qibing Zhou: Huazhong University of Science and Technology
HaiFang Yin: Tianjin Medical University

Nature Communications, 2020, vol. 11, issue 1, 1-16

Abstract: Abstract Treating large established tumors is challenging for dendritic cell (DC)-based immunotherapy. DC activation with tumor cell-derived exosomes (TEXs) carrying multiple tumor-associated antigen can enhance tumor recognition. Adding a potent adjuvant, high mobility group nucleosome-binding protein 1 (HMGN1), boosts DCs’ ability to activate T cells and improves vaccine efficiency. Here, we demonstrate that TEXs painted with the functional domain of HMGN1 (TEX-N1ND) via an exosomal anchor peptide potentiates DC immunogenicity. TEX-N1ND pulsed DCs (DCTEX-N1ND) elicit long-lasting antitumor immunity and tumor suppression in different syngeneic mouse models with large tumor burdens, most notably large, poorly immunogenic orthotopic hepatocellular carcinoma (HCC). DCTEX-N1ND show increased homing to lymphoid tissues and contribute to augmented memory T cells. Importantly, N1ND-painted serum exosomes from cancer patients also promote DC activation. Our study demonstrates the potency of TEX-N1ND to strengthen DC immunogenicity and to suppress large established tumors, and thus provides an avenue to improve DC-based immunotherapy.

Date: 2020
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DOI: 10.1038/s41467-020-15569-2

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