Localized cocktail chemoimmunotherapy after in situ gelation to trigger robust systemic antitumor immune responses
Localized cocktail chemoimmunotherapy after in situ gelation to trigger robust systemic antitumor immune responses
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DOI：
10.1126/sciadv.aaz4204
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发表时间：
2020-03-01
期刊：
影响因子：
13.6
通讯作者：
Liu, Zhuang
中科院分区：
文献类型：
--
作者：
Chao, Yu;Liang, Chao;Liu, Zhuang
目前，对于开发具有降低的全身毒性和有效的化学免疫疗法来对抗扩散转移的晚期癌症有巨大的需求。在这里，我们报告了几种“鸡尾酒”治疗配方，通过将免疫原性细胞死亡（ICD）诱导化疗药物和免疫佐剂与藻酸盐（ALG）混合在一起进行局部化学免疫治疗。免疫检查点阻断（ICB）抗体可以包含在该混合物中用于局部注射或通过常规静脉注射使用。将这种混合物注射到实体瘤中后，ALG 的原位凝胶化将导致治疗药物的局部保留和持续释放，以减少全身毒性。化疗诱导的ICD在免疫佐剂的帮助下会触发肿瘤特异性免疫反应，ICB进一步放大这种免疫反应，引发有效的全身抗肿瘤免疫反应，破坏局部肿瘤，消除转移和抑制癌症复发。我们联合临床使用的药物进行肿瘤局部鸡尾酒化学免疫治疗的策略具有巨大的临床转化潜力。
Currently, there is a huge demand to develop chemoimmunotherapy with reduced systemic toxicity and potent efficacy to combat late-stage cancers with spreading metastases. Here, we report several "cocktail" therapeutic formulations by mixing immunogenic cell death (ICD)-inducing chemotherapeutics and immune adjuvants together with alginate (ALG) for localized chemoimmunotherapy. Immune checkpoint blockade (ICB) antibody may be either included into this cocktail for local injection or used via conventional intravenous injection. After injection of such cocktail into a solid tumor, in-situ gelation of ALG would lead to local retention and sustained release of therapeutics to reduce systemic toxicity. The chemotherapy-induced ICD with the help of immune adjuvant would trigger tumor-specific immune responses, which are further amplified by ICB to elicit potent systemic antitumor immune responses in destructing local tumors, eliminating metastases and inhibiting cancer recurrence.Our strategy of combining clinically used agents for tumor-localized cocktail chemoimmunotherapy possesses great potential for clinical translation.