2. Academic Validation
  3. Alarmin-painted exosomes elicit persistent antitumor immunity in large established tumors in mice

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

  • Nat Commun. 2020 Apr 14;11(1):1790. doi: 10.1038/s41467-020-15569-2.
Bingfeng Zuo 1,  Han Qi 1,  Zhen Lu 1,  Lu Chen 2,  Bo Sun 3,  Rong Yang 4,  Yang Zhang 1,  Zhili Liu 1,  Xianjun Gao 1,  Abin You 1,  Li Wu 1,  Renwei Jing 1,  Qibing Zhou 4,  HaiFang Yin 5
Affiliations

Affiliations

  • 1 Key Laboratory of Immune Microenvironment and Disease (Ministry of Education) & Tianjin Key Laboratory of Cellular Homeostasis and Human Diseases & Department of Cell Biology, Tianjin Medical University, Qixiangtai Road, Heping District, Tianjin, 300070, China.
  • 2 Department of Hepatobiliary, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin, 300060, China.
  • 3 Department of The Second Department of Breast Cancer, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin, 300060, China.
  • 4 Department of Nanomedicine & Biopharmaceuticals, National Engineering Research Center for Nanomedicine, Huazhong University of Science and Technology, Wuhan, 430074, Hubei Province, China.
  • 5 Key Laboratory of Immune Microenvironment and Disease (Ministry of Education) & Tianjin Key Laboratory of Cellular Homeostasis and Human Diseases & Department of Cell Biology, Tianjin Medical University, Qixiangtai Road, Heping District, Tianjin, 300070, China. [email protected].
PMID: 32286296 DOI: 10.1038/s41467-020-15569-2
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.

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