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A biodegradable thermosensitive hydrogel vaccine for cancer immunotherapy
Applied Materials Today ( IF 8.3 ) Pub Date : 2020-03-03 , DOI: 10.1016/j.apmt.2020.100608
Fan Yang , Kun Shi , Yanpeng Jia , Ying Hao , Jinrong Peng , Liping Yuan , Yu Chen , Meng Pan , Zhiyong Qian

Although existing nanomaterial-based strategies for the recruitment and activation of dendritic cells (DCs) for cancer immunotherapy have achieved promising results, many issues related to safety and effectiveness remain unresolved. Simpler and safer designs are thus urgently required to eradicate tumors. In this study, we engineered an injectable and biodegradable thermosensitive hydrogel vaccine encapsulating GM-CSF, CpG-ODN (a TLR 9 agonist) and tumor cell lysates (TLs). The results confirm that this formulation of the vaccine can significantly activate and mature DCs both in vitro and in vivo due to its ability to release immunomodulators and antigens in a sustained manner. Surprisingly, on day 14, compared to controls, the hydrogel vaccine maintained a higher level of tumor necrosis factor (TNF) in the serum, which suggested it promoted a direct killing effect on tumors. When B16F10 or C26 tumors were immunized with TLs, the hydrogel vaccine observably delayed tumor growth and prolonged overall survival time in both prophylactic and therapeutic trials. In addition, an optimal formulation of this system was established to achieve the most effective inhibition of tumors. Our findings suggest that this hydrogel system may serve as an easily manufactured vaccine delivery platform for cancer immunotherapy.



中文翻译:

用于癌症免疫治疗的可生物降解的热敏水凝胶疫苗

尽管现有的基于纳米材料的,用于癌症免疫疗法的树突状细胞(DC)募集和激活的策略已取得了可喜的成果,但许多与安全性和有效性相关的问题仍未解决。因此,迫切需要更简单,更安全的设计来根除肿瘤。在这项研究中,我们设计了一种可注射且可生物降解的热敏性水凝胶疫苗,其中包封了GM-CSF,CpG-ODN(TLR 9激动剂)和肿瘤细胞裂解液(TLs)。结果证实,这种疫苗制剂可以在体外体内显着激活并成熟DC 由于其能够持续释放免疫调节剂和抗原的能力。出乎意料的是,与对照相比,在第14天,水凝胶疫苗在血清中维持较高水平的肿瘤坏死因子(TNF),这表明它促进了对肿瘤的直接杀伤作用。当B16F10或C26肿瘤用TL免疫后,在预防和治疗试验中,水凝胶疫苗可观察到延迟肿瘤生长并延长总生存时间。另外,建立了该系统的最佳制剂以实现最有效的肿瘤抑制。我们的发现表明,这种水凝胶系统可以用作癌症免疫疗法的易于制造的疫苗输送平台。

更新日期:2020-03-03
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