Tailored Polymers with Complement Activation Ability To Improve Antitumor Immunity
Tailored Polymers with Complement Activation Ability To Improve Antitumor Immunity
复制标题
具有补体激活能力的定制聚合物可提高抗肿瘤免疫力
DOI：
10.1021/acs.molpharmaceut.9b00195
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发表时间：
2019
影响因子：
4.9
通讯作者：
Dawei Chen
中科院分区：
文献类型：
--
作者：
Chenxi Li;Yue Lu;Qing Chen;Haiyang Hu;Xiuli Zhao;Mingxi Qiao;Dawei Chen
补体系统在宿主天然免疫中起着重要作用，其激活可作为疫苗佐剂的潜在策略。本文中，使用羧基改性的聚（2-乙基-2-恶唑啉）-聚（d，l-丙交酯）的二嵌段共聚物（COOH-PEOz-PLA）开发pH响应性胶束疫苗平台（COOH-NPs）。该共聚物自组装成表面具有羟基屏蔽的胶束，其激活补体系统以增强免疫应答。与对照纳米颗粒（OCH 3-NPs）相比，COOH-NPs显著增强了淋巴结驻留树突状细胞成熟、抗原特异性IgG产生、抗原特异性CD 4+和CD 8 + T细胞活化以及体内记忆T细胞生成量。此外，在E. G7-OVA荷瘤小鼠中用COOH-NPs/OVA免疫不仅显著抑制肿瘤生长，而且延长荷瘤小鼠的存活。这些结果表明，具有补体激活能力的COOH-NPs有效地增强了免疫应答以发挥抗肿瘤作用。该研究证明了利用补体激活疫苗平台进行癌症免疫治疗的重要性。
The complement system plays an important role in host innate immunity, and its activation can be exploited as a potential strategy for vaccine adjuvants. Herein, a pH-responsive micellar vaccine platform (COOH-NPs) was developed using a carboxyl-modified diblock copolymer of poly(2-ethyl-2-oxazoline)-poly(d,l-lactide) (COOH-PEOz-PLA). The copolymer self-assembled into micelles with hydroxyl groups shielding on the surface, which activated the complement system for the enhanced immune responses. Compared with the control nanoparticles (OCH3-NPs), COOH-NPs significantly enhanced lymph node-resident dendritic cell maturation, antigen-specific IgG production, antigen-specific CD4+and CD8+T-cell activation, and the amount of memory T-cell generation in vivo. Furthermore, immunization with COOH-NPs/OVA in E.G7-OVA tumor-bearing mice not only remarkably inhibited tumor growth but also prolonged the survival of tumor-bearing mice. These results indicated that COOH-NPs with the capability of complement activation efficiently boosted the immune responses for the antitumor effect. The study demonstrated the significance of taking advantage of a complement-activating vaccine platform for cancer immunotherapy.