Combination delivery of TGF-β inhibitor and IL-2 by nanoscale liposomal polymeric gels enhances tumour immunotherapy.
Combination delivery of TGF-β inhibitor and IL-2 by nanoscale liposomal polymeric gels enhances tumour immunotherapy.
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肿瘤微环境通过多种免疫机制阻碍常规免疫治疗，例如转化生长因子-β（TGF-β）的分泌，其阻碍局部肿瘤免疫应答。因此，高剂量的白细胞介素-2（IL-2）（一种用于转移性黑色素瘤的常规细胞因子）仅诱导有限的反应。为了克服肿瘤微环境的免疫抑制性质，我们开发了药物复合的环糊精和包封细胞因子的可生物降解聚合物的纳米级脂质体聚合物凝胶（纳米脂质体凝胶; nLG），可以持续递送小疏水性分子抑制剂和水溶性蛋白质细胞因子到肿瘤微环境。释放TGF-β抑制剂和IL-2的nLG显著延迟肿瘤生长，增加荷瘤小鼠的存活率，并增加自然杀伤细胞和肿瘤内活化的CD 8 + T细胞浸润的活性。我们证明了nLGs在肿瘤免疫治疗中的功效来自于涉及先天性和适应性免疫应答的激活的关键机制。
The tumour microenvironment thwarts conventional immunotherapy through multiple immunologic mechanisms, such as the secretion of the transforming growth factor-β (TGF-β), which stunts local tumour immune responses. Therefore, high doses of interleukin-2 (IL-2), a conventional cytokine for metastatic melanoma, induces only limited responses. To overcome the immunoinhibitory nature of the tumour microenvironment, we developed nanoscale liposomal polymeric gels (nanolipogels; nLGs) of drug-complexed cyclodextrins and cytokine-encapsulating biodegradable polymers that can deliver small hydrophobic molecular inhibitors and water-soluble protein cytokines in a sustained fashion to the tumour microenvironment. nLGs releasing TGF-β inhibitor and IL-2 significantly delayed tumour growth, increased survival of tumour-bearing mice, and increased the activity of natural killer cells and of intratumoral-activated CD8+ T-cell infiltration. We demonstrate that the efficacy of nLGs in tumour immunotherapy results from a crucial mechanism involving activation of both innate and adaptive immune responses.
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影响因子：
17.1
作者：
Meng H;Liong M;Xia T;Li Z;Ji Z;Zink JI;Nel AE
通讯作者：
Nel AE
影响因子：
3.6
作者：
Byfield, SD;Major, C;Roberts, AB
通讯作者：
Roberts, AB
DOI：
10.1073/pnas.0909384107
发表时间：
2010-02-02
影响因子：
11.1
作者：
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通讯作者：
Boyman, Onur
DOI：
10.1073/pnas.0601755103
发表时间：
2006-04-18
影响因子：
11.1
作者：
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通讯作者：
Langer, R
影响因子：
10.8
作者：
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通讯作者：
Hirano, K