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In situ sprayed bioresponsive immunotherapeutic gel for post-surgical cancer treatment
Nature Nanotechnology ( IF 38.3 ) Pub Date : 2018-12-10 , DOI: 10.1038/s41565-018-0319-4
Qian Chen , Chao Wang , Xudong Zhang , Guojun Chen , Quanyin Hu , Hongjun Li , Jinqiang Wang , Di Wen , Yuqi Zhang , Yifei Lu , Guang Yang , Chen Jiang , Jun Wang , Gianpietro Dotti , Zhen Gu

Cancer recurrence after surgical resection remains a significant cause of treatment failure. Here, we have developed an in situ formed immunotherapeutic bioresponsive gel that controls both local tumour recurrence after surgery and development of distant tumours. Briefly, calcium carbonate nanoparticles pre-loaded with the anti-CD47 antibody are encapsulated in the fibrin gel and scavenge H+ in the surgical wound, allowing polarization of tumour-associated macrophages to the M1-like phenotype. The released anti-CD47 antibody blocks the ‘don’t eat me’ signal in cancer cells, thereby increasing phagocytosis of cancer cells by macrophages. Macrophages can promote effective antigen presentation and initiate T cell mediated immune responses that control tumour growth. Our findings indicate that the immunotherapeutic fibrin gel ‘awakens’ the host innate and adaptive immune systems to inhibit both local tumour recurrence post surgery and potential metastatic spread.



中文翻译:

原位喷雾生物反应性免疫治疗凝胶用于手术后癌症治疗

手术切除后的癌症复发仍然是治疗失败的重要原因。在这里,我们开发了一种原位形成的免疫治疗生物反应性凝胶,可控制手术后局部肿瘤的复发和远处肿瘤的发展。简而言之,将预装有抗CD47抗体的碳酸钙纳米颗粒封装在血纤蛋白凝胶中,并清除H +在手术伤口中,使肿瘤相关的巨噬细胞极化为M1样表型。释放的抗CD47抗体阻断了癌细胞中的“不要吃我”信号,从而增加了巨噬细胞对癌细胞的吞噬作用。巨噬细胞可以促进有效的抗原呈递并启动控制肿瘤生长的T细胞介导的免疫反应。我们的发现表明,免疫治疗性纤维蛋白凝胶可“唤醒”宿主的先天和适应性免疫系统,以抑制术后局部肿瘤复发和潜在的转移扩散。

更新日期:2018-12-11
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