Nanocage‐Therapeutics Prevailing Phagocytosis and Immunogenic Cell Death Awakens Immunity against Cancer,Advanced Materials

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Nanocage‐Therapeutics Prevailing Phagocytosis and Immunogenic Cell Death Awakens Immunity against Cancer
Advanced Materials ( IF 27.4 ) Pub Date : 2018-01-15 , DOI: 10.1002/adma.201705581
Eun Jung Lee _{1,

2} , Gi-Hoon Nam _{2,

3} , Na Kyeong Lee _{2,

4} , Minwoo Kih _{2,

3} , Eunee Koh _{2,

3} , Yoon Kyoung Kim _{2,

3} , Yeonsun Hong _{2,

3} , Soyoun Kim ₅ , Seung-Yoon Park ₆ , Cherlhyun Jeong ₂ , Yoosoo Yang ₂ , In-San Kim _{2,

3}

Affiliation

A growing appreciation of the relationship between the immune system and the tumorigenesis has led to the development of strategies aimed at “re‐editing” the immune system to kill tumors. Here, a novel tactic is reported for overcoming the activation‐energy threshold of the immunosuppressive tumor microenvironment and mediating the delivery and presentation of tumor neoantigens to the host's immune system. This nature‐derived nanocage not only efficiently presents ligands that enhance cancer cell phagocytosis, but also delivers drugs that induce immunogenic cancer cell death. The designed nanocage‐therapeutics induce the release of neoantigens and danger signals in dying tumor cells, and leads to enhancement of tumor cell phagocytosis and cross‐priming of tumor specific T cells by neoantigen peptide‐loaded antigen‐presenting cells. Potent inhibition of tumor growth and complete eradication of tumors is observed through systemic tumor‐specific T cell responses in tumor draining lymph nodes and the spleen and further, infiltration of CD8+ T cells into the tumor site. Remarkably, after removal of the primary tumor, all mice treated with this nanocage‐therapeutics are protected against subsequent challenge with the same tumor cells, suggesting development of lasting, tumor‐specific responses. This designed nanocage‐therapeutics “awakens” the host's immune system and provokes a durable systemic immune response against cancer.

中文翻译：

吞噬作用和免疫原性细胞死亡的纳米笼疗法唤醒了抵抗癌症的免疫力。

对免疫系统与肿瘤发生之间关系的日益增长的认识导致了旨在“重新编辑”免疫系统以杀死肿瘤的策略的发展。在这里，据报道有一种新的策略可以克服免疫抑制性肿瘤微环境的激活能阈值，并介导肿瘤新抗原向宿主免疫系统的传递和呈递。这种源自自然界的纳米笼子不仅有效地呈现了增强癌细胞吞噬作用的配体，而且还提供了诱导免疫原性癌细胞死亡的药物。设计的纳米笼疗法可诱导垂死的肿瘤细胞释放新抗原和危险信号，并通过负载新抗原肽的抗原呈递细胞增强肿瘤细胞的吞噬作用和肿瘤特异性T细胞的交叉启动。通过在肿瘤引流淋巴结和脾脏中的全身性肿瘤特异性T细胞反应，以及进一步的CD8 + T细胞浸润到肿瘤部位，可以观察到对肿瘤生长的有效抑制和对肿瘤的彻底根除。值得注意的是，在切除原发肿瘤后，所有接受这种纳米笼治疗剂治疗的小鼠均受到保护，不会再受到相同肿瘤细胞的攻击，这表明它们会产生持久的肿瘤特异性反应。这种设计的纳米笼疗法可“唤醒”宿主的免疫系统，并引发针对癌症的持久性全身免疫反应。去除原发肿瘤后，所有接受这种纳米笼治疗剂治疗的小鼠均受到保护，以防止随后受到相同肿瘤细胞的攻击，这表明可以产生持久的肿瘤特异性反应。这种设计的纳米笼疗法可“唤醒”宿主的免疫系统，并引发针对癌症的持久性全身免疫反应。去除原发肿瘤后，所有接受这种纳米笼治疗剂治疗的小鼠均受到保护，以防止随后受到相同肿瘤细胞的攻击，这表明可以产生持久的肿瘤特异性反应。这种设计的纳米笼疗法可“唤醒”宿主的免疫系统，并引发针对癌症的持久性全身免疫反应。

更新日期：2018-01-15

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