A tumor‐targeting nano‐adjuvant for in situ vaccine based on ultrasound therapy

Ultrasound‐generated antigens combined with TLR7/8 agonists as adjuvants have demonstrated significant anti‐tumor efficacy as an in‐situ vaccine. However, the use of TLR7/8 agonists can cause severe inflammatory responses. In this study, we present a novel tumor‐targeting nano‐adjuvant termed aPDL1‐...

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Bibliographic Details
Published in:Aggregate (Hoboken) 2024-06, Vol.5 (3), p.n/a
Main Authors: Cui, Linjie, Yao, Haochen, Xue, Fuxin, Sun, Jiali, Ren, Xitong, Zheng, Mengfei, Liu, Zhilin, Tang, Zhaohui
Format: Article
Language:English
Subjects:
immunotherapy
in situ vaccine
R848 nanoparticles
tumor‐targeting
ultrasound therapy
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Summary:Ultrasound‐generated antigens combined with TLR7/8 agonists as adjuvants have demonstrated significant anti‐tumor efficacy as an in‐situ vaccine. However, the use of TLR7/8 agonists can cause severe inflammatory responses. In this study, we present a novel tumor‐targeting nano‐adjuvant termed aPDL1‐PLG/R848 NPs, which are composed of aPDL1 antibody, Fc‐III‐4C peptide linker (Fc‐linker) and poly(L‐glutamic acid)‐grafted‐R848. Under ultrasound irradiation, antigen‐presenting cells activate immune mechanisms in vivo under dual stimulation of in situ antigens and immune adjuvants. The strategy inhibits primary tumor growth and induces a strong antigen‐specific immune memory effect to prevent tumor recurrence in vivo. This work offers a safe and potent platform for an in situ cancer vaccine based on ultrasound therapy. Ultrasound therapy induces in situ vaccination (ISV) by promoting tumor immunogenic death, and the tumor‐targeting nano‐adjuvant (aPDL1‐PLG/R848 NPs) enhances the ISV effect by tumor‐targeted delivery of R848, minimizing side effects. This synergy triggers a robust systemic antitumor immune response for in situ cancer vaccination.
ISSN:2692-4560
2692-4560
DOI:10.1002/agt2.504