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A lyophilizable LNP vaccine enables STING-reinforced postoperational adjuvant immunotherapy

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机构: [1]The NMPA and State Key Laboratory of Respiratory Disease, School of Pharmaceutical Sciences, Department of Emergency, the Second Affiliated Hospital, Guangzhou Medical University, Guangzhou 511436, P. R. China [2]Yunnan Digestive Endoscopy Clinical Medical Center, Department of Gastroenterology, The First People’s Hospital of Yunnan Province, Affiliated Hospital of Kunming University of Science and Technology, Kunming 650032, P. R. China [3]Graduate School of Biomedical Engineering, ARC Centre of Excellence in Nanoscale Biophotonics, Faculty of Engineering, UNSW Sydney, Sydney, NSW 2052, Australia [4]School of Biomedical Engineering, University of Technology Sydney, Ultimo, NSW 2007, Australia
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关键词: Lyophilizable LNP vaccine iCBT Adjuvant therapy STING Manganese

摘要:
Immune checkpoint blockade therapy (iCBT) has revolutionized cancer treatment, however, there is a low response rate, especially in treating postsurgical reoccurring tumors. Vaccine based immunotherapy can sensitize iCBT, but its development was largely hindered by inefficient delivery and high requirements of storage. In this study, the vaccine loaded with immunostimulant was employed to improve iCBT-based adjuvant postsurgical therapy. A lyophilized, antigen E7 peptide and manganese ion (Mn2+) co-delivered tumor vaccine was developed based on lipid nanoparticles (EM@LNP). The vaccination efficacy was examined in both prophylactic and therapeutic schemes in murine subcutaneous models, the synergetic effect of vaccination combined with anti-PD-1 therapy was further investigated in post-operative tumor model. EM@LNP vaccination elicited effective CD8+T cell response through modulating tumor immunosuppressive microenvironment and conferring immune memory, demonstrating potent immunization in both preventive and therapeutic schemes. What's more, EM@LNP vaccination orchestrated with iCBT, efficiently repressing tumor recurrence. Further mechanism studies using inhibitor for cells invitro and the investigation using STING-/- mice confirmed that the cGAS-STING signaling pathway activated by Mn2+ is indispensable for LNP vaccination and the coordination with iCBT-based adjuvant immunotherapy. In summary, this study shows a lyophilized LNP vaccine could significantly amplify iCBT efficiency, providing a translational strategy of adjuvant immunotherapy for treating postsurgical tumor recurrence.

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大类 | 1 区 生物学
小类 | 1 区 生物工程与应用微生物 2 区 纳米科技
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Q1 BIOTECHNOLOGY & APPLIED MICROBIOLOGY Q1 NANOSCIENCE & NANOTECHNOLOGY

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第一作者机构: [1]The NMPA and State Key Laboratory of Respiratory Disease, School of Pharmaceutical Sciences, Department of Emergency, the Second Affiliated Hospital, Guangzhou Medical University, Guangzhou 511436, P. R. China
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