Modular Hydrogel Vaccine for Programmable and Coordinate Elicitation of Cancer Immunotherapy,Advanced Science

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Modular Hydrogel Vaccine for Programmable and Coordinate Elicitation of Cancer Immunotherapy
Advanced Science ( IF 14.3 ) Pub Date : 2023-05-24 , DOI: 10.1002/advs.202301789
Panpan Ji ₁ , Wenqi Sun ₂ , Siyan Zhang ₂ , Yuqi Xing ₃ , Chen Wang ₂ , Mengying Wei ₃ , Qiuyun Li ₄ , Gang Ji ₁ , Guodong Yang ₃

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Immunotherapy holds great promise for the treatment of malignant cancer. However, the lack of sufficient tumor neoantigens and incomplete dendritic cell (DC) maturation compromise the efficacy of immunotherapy. Here, a modular hydrogel-based vaccine capable of eliciting a powerful and sustained immune response is developed. Briefly, CCL21a and Exo^GM-CSF+Ce6 (tumor cell-derived exosomes with granulocyte-macrophage colony-stimulating factor (GM-CSF) mRNA encapsulated inside and sonosensitizer chlorin e6 (Ce6) incorporated in the surface) are mixed with nanoclay and gelatin methacryloyl, forming the hydrogel designated as CCL21a/Exo^GM-CSF+Ce6@nanoGel. The engineered hydrogel releases CCL21a and GM-CSF with a time gap. The earlier released CCL21a diverts the tumor-draining lymph node (TdLN) metastatic tumor cells to the hydrogel. Consequently, the trapped tumor cells in the hydrogel, in turn, engulf the Ce6-containing exosomes and thus are eradicated by sonodynamic therapy (SDT), serving as the antigen source. Later, together with the remnant CCL21a, GM-CSF produced by cells engulfing Exo^GM-CSF+Ce6 continuously recruits and provokes DCs. With the two programmed modules, the engineered modular hydrogel vaccine efficiently inhibits tumor growth and metastasis via diverting TdLN metastatic cancer to hydrogel, killing the trapped tumor cells, and eliciting prolonged and powerful immunotherapy in an orchestrated manner. The strategy would open an avenue for cancer immunotherapy.

中文翻译：

用于可编程和协调引发癌症免疫治疗的模块化水凝胶疫苗

免疫疗法对于治疗恶性癌症具有广阔的前景。然而，缺乏足够的肿瘤新抗原和树突状细胞（DC）成熟不完全会损害免疫疗法的疗效。在这里，开发了一种基于模块化水凝胶的疫苗，能够引发强大且持续的免疫反应。简而言之，将 CCL21a 和 Exo ^GM-CSF+Ce6（肿瘤细胞衍生的外泌体，内部封装有粒细胞巨噬细胞集落刺激因子 (GM-CSF) mRNA，表面掺入声敏剂二氢卟酚 e6 (Ce6)）与纳米粘土和明胶混合甲基丙烯酰，形成水凝胶，命名为 CCL21a/Exo ^GM-CSF+Ce6 @nanoGel。工程水凝胶以一定的时间间隔释放 CCL21a 和 GM-CSF。早期发布的 CCL21a 将肿瘤引流淋巴结 (TdLN) 转移性肿瘤细胞转移到水凝胶中。因此，水凝胶中捕获的肿瘤细胞反过来吞噬含有 Ce6 的外泌体，从而被作为抗原来源的声动力疗法 (SDT) 根除。^{随后，吞噬 Exo GM-CSF+Ce6}的细胞产生的 GM-CSF 与残余的 CCL21a 一起不断招募并激发 DC。通过这两个编程模块，工程化模块化水凝胶疫苗通过将 TdLN 转移性癌症转移到水凝胶中，杀死被捕获的肿瘤细胞，并以精心策划的方式引发持久而强大的免疫治疗，从而有效抑制肿瘤生长和转移。该策略将为癌症免疫治疗开辟一条途径。

更新日期：2023-05-24

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