Many favorable anticancer treatments owe their success to the induction immunogenic cell death (ICD) in cancer cells, which results in the release of endogenous danger signals along with tumor antigens for effective priming of anticancer immunity. We describe a strategy to artificially induce ICD by delivering the agonist of stimulator of interferon genes (STING) into tumor cells using hollow polymeric nanoshells. Following intracellular delivery of exogenous adjuvant, subsequent cytotoxic treatment creates immunogenic cellular debris that spatiotemporally coordinate tumor antigens and STING agonist in a process herein termed synthetic immunogenic cell death (sICD). sICD is indiscriminate to the type of chemotherapeutics and enables colocalization of exogenously administered immunologic adjuvants and tumor antigens for enhanced antigen presentation and anticancer adaptive response. In three mouse tumor models, sICD enhances therapeutic efficacy and restrains tumor progression. The study highlights the benefit of delivering STING agonists to cancer cells, paving ways to new chemo-immunotherapeutic designs.

中文翻译：

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STING激动剂纳米壳的细胞内传递介导的合成免疫原性细胞死亡增强抗癌化学免疫疗法。

许多成功的抗癌治疗方法都得益于癌细胞中诱导免疫原性细胞死亡（ICD）的成功，从而导致内源性危险信号与肿瘤抗原一起释放，从而有效引发抗癌免疫力。我们描述了一种通过使用空心聚合物纳米壳将干扰素基因（STING）的激动剂传递到肿瘤细胞中来人工诱导ICD的策略。在细胞内递送外源性佐剂之后，随后的细胞毒性处理在本文称为合成免疫原性细胞死亡（sICD）的过程中时空协调肿瘤抗原和STING激动剂的免疫原性细胞碎片。sICD不受化学疗法类型的影响，可以使外源性免疫佐剂和肿瘤抗原共定位，从而增强抗原呈递和抗癌适应性反应。在三种小鼠肿瘤模型中，sICD可增强治疗功效并抑制肿瘤进展。这项研究强调了将STING激动剂提供给癌细胞的好处，为新的化学免疫疗法设计铺平了道路。