不含抗原/佐剂的脂质体诱导增强癌症免疫疗法的佐剂效应

Exploration Pub Date : 2024-07-17 DOI:10.1002/exp.20230115
Qianqian Guo, Xiaoxuan Xu, Xiaojiang Lai, Jialin Duan, Dan Yan, Dangge Wang
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摘要

癌症疫苗通过提供抗原和佐剂来激发宿主免疫力,有望治疗恶性肿瘤。除了铝佐剂外,脂质体还通过调节有效载荷的积累、内化和释放,显示出高效的佐剂效应。然而,在没有抗原和佐剂的情况下,脂质体是否会产生内在佐剂效应仍是未知数。在此,我们开发了一个表面电荷可变的无抗原/佐剂脂质体库,发现高阴离子脂质体在增强免疫反应方面表现出良好的佐剂效果。阴离子脂质体能调动树突状细胞(DC)的 MyD88 通路,激活 T 辅助细胞和 CD8+ T 细胞。阴离子脂质体通过调节 Th1、Th2 和调节性 T 细胞(Tregs)的数量来增强宿主的免疫力,并以良好的生物安全性增强淋巴器官中的适应性 CD8+ T 细胞。在小鼠体内同时注射抗原和阴离子脂质体后,它能最有效地保护小鼠免受 MC38 大肠癌的侵袭。总之,这项研究揭示了脂质体的表面电荷会影响其佐剂效率,并为增强免疫提供了一种阴离子纳米佐剂配方。
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Antigen/adjuvant‐free liposome induces adjuvant effects for enhancing cancer immunotherapy
Cancer vaccines are promising to treat malignancy by delivering antigens and adjuvants to elicit host immunity. Beyond aluminum adjuvants, liposomes show efficient adjuvant effects through regulating the accumulation, internalization and release of payloads. However, it remains unknown that whether the liposome will perform intrinsic adjuvant effects in the absence of antigens and adjuvants. Herein, a library of antigen/adjuvant‐free liposomes with variable surface charges has been developed and it has been found that highly anionic liposomes show promising adjuvant effects for boosting immune responses. The anionic liposome mobilizes the MyD88 pathways of dendritic cells (DCs) to activate T helper cells and CD8+ T cells. The anionic liposomes enhance host immunity by regulating the population of Th1, Th2 and regulatory T cells (Tregs), and boost adaptive CD8+ T cells in lymphoid organs with good biosafety. It shows the most efficient protection against MC38 colorectal cancer in mice after a parallel injection of antigens and anionic liposomes. Overall, this study reveals that the surface charge of liposome affects its adjuvant efficiency and provides an anionic nanosized adjuvant formulation for enhancing immunization.
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