<br>免疫调节性锌明矾/卵清蛋白纳米疫苗通过红细胞辅助级联免疫激活促进癌症金属免疫治疗,Advanced Science

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免疫调节性锌明矾/卵清蛋白纳米疫苗通过红细胞辅助级联免疫激活促进癌症金属免疫治疗
Advanced Science ( IF 14.3 ) Pub Date : 2023-12-08 , DOI: 10.1002/advs.202307389
Jing Zhao ₁ , Lingxiao Zhang ₂ , Pin Li ₁ , Shanbiao Liu ₁ , Shiyi Yu ₁ , Zheng Chen ₁ , Mingjian Zhu ₁ , Shangzhi Xie ₁ , Daishun Ling _{1,

3,

4} , Fangyuan Li _{1,

4,

5}

Affiliation

癌症治疗疫苗是激活免疫系统和引发针对肿瘤的保护性反应的强大工具。然而，它们的功效常常受到免疫反应薄弱和缓慢的阻碍。在这里，作者介绍了一种免疫策略，利用衰老红细胞通过暂时饱和肝脏巨噬细胞来促进免疫调节性锌明矾/卵清蛋白 (ZAlum/OVA) 纳米疫苗在脾脏和实体瘤内的积累。这种方法为通过级联免疫激活增强癌症金属免疫疗法奠定了基础。 ZAlum/OVA 纳米疫苗在脾脏中的积累显着增强了树突状细胞中自噬依赖性抗原的呈递，快速启动针对实体瘤的 OVA 特异性 T 细胞反应。同时，在肿瘤微环境中积累的 ZAlum/OVA 纳米疫苗会触发免疫原性细胞死亡，从而诱导个体化肿瘤相关抗原特异性 T 细胞反应并增加 T 细胞浸润。这种使用 ZAlum/OVA 纳米疫苗的红细胞辅助级联免疫激活可导致快速而强大的抗肿瘤免疫诱导，在临床癌症金属免疫治疗中具有巨大潜力。

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An Immunomodulatory Zinc-Alum/Ovalbumin Nanovaccine Boosts Cancer Metalloimmunotherapy Through Erythrocyte-Assisted Cascade Immune Activation

Cancer therapeutic vaccines are powerful tools for immune system activation and eliciting protective responses against tumors. However, their efficacy has often been hindered by weak and slow immune responses. Here, the authors introduce an immunization strategy employing senescent erythrocytes to facilitate the accumulation of immunomodulatory zinc-Alum/ovalbumin (ZAlum/OVA) nanovaccines within both the spleen and solid tumors by temporarily saturating liver macrophages. This approach sets the stage for boosted cancer metalloimmunotherapy through a cascade immune activation. The accumulation of ZAlum/OVA nanovaccines in the spleen substantially enhances autophagy-dependent antigen presentation in dendritic cells, rapidly initiating OVA-specific T-cell responses against solid tumors. Concurrently, ZAlum/OVA nanovaccines accumulated in the tumor microenvironment trigger immunogenic cell death, leading to the induction of individualized tumor-associated antigen-specific T cell responses and increased T cell infiltration. This erythrocyte-assisted cascade immune activation using ZAlum/OVA nanovaccines results in rapid and robust antitumor immunity induction, holding great potential for clinical cancer metalloimmunotherapy.

更新日期：2023-12-08

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