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原位喷涂生物响应免疫治疗凝胶用于术后癌症治疗。

In situ sprayed bioresponsive immunotherapeutic gel for post-surgical cancer treatment.

机构信息

Department of Bioengineering, University of California, Los Angeles, CA, USA.

California NanoSystems Institute, University of California, Los Angeles, CA, USA.

出版信息

Nat Nanotechnol. 2019 Jan;14(1):89-97. doi: 10.1038/s41565-018-0319-4. Epub 2018 Dec 10.

Abstract

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.

摘要

手术后癌症复发仍然是治疗失败的一个重要原因。在这里,我们开发了一种原位形成的免疫治疗生物响应性凝胶,它可以控制手术后局部肿瘤复发和远处肿瘤的发展。简而言之,预先加载有抗 CD47 抗体的碳酸钙纳米粒子被包裹在纤维蛋白凝胶中,并清除手术伤口中的 H,从而使肿瘤相关巨噬细胞向 M1 样表型极化。释放的抗 CD47 抗体阻断了癌细胞中的“别吃我”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 T 细胞介导的免疫反应,从而控制肿瘤生长。我们的研究结果表明,免疫治疗纤维蛋白凝胶“唤醒”了宿主固有和适应性免疫系统,以抑制手术后局部肿瘤复发和潜在的转移扩散。

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