CAS Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety & CAS Center for Excellence in Nanoscience, National Center for Nanoscience and Technology of China, Zhongguancun, Beijing, China.
Center of Materials Science and Optoelectronics Engineering, University of Chinese Academy of Sciences, Beijing, China.
Nat Commun. 2021 Apr 6;12(1):2041. doi: 10.1038/s41467-021-22308-8.
An effective tumor vaccine vector that can rapidly display neoantigens is urgently needed. Outer membrane vesicles (OMVs) can strongly activate the innate immune system and are qualified as immunoadjuvants. Here, we describe a versatile OMV-based vaccine platform to elicit a specific anti-tumor immune response via specifically presenting antigens onto OMV surface. We first display tumor antigens on the OMVs surface by fusing with ClyA protein, and then simplify the antigen display process by employing a Plug-and-Display system comprising the tag/catcher protein pairs. OMVs decorated with different protein catchers can simultaneously display multiple, distinct tumor antigens to elicit a synergistic antitumour immune response. In addition, the bioengineered OMVs loaded with different tumor antigens can abrogate lung melanoma metastasis and inhibit subcutaneous colorectal cancer growth. The ability of the bioengineered OMV-based platform to rapidly and simultaneously display antigens may facilitate the development of these agents for personalized tumour vaccines.
我们迫切需要一种能够快速展示新抗原的有效肿瘤疫苗载体。外膜囊泡（OMVs）可以强烈激活先天免疫系统，有资格作为免疫佐剂。在这里，我们描述了一种基于 OMV 的多功能疫苗平台，通过将抗原特异性地展示在 OMV 表面来引发特异性的抗肿瘤免疫反应。我们首先通过与 ClyA 蛋白融合将肿瘤抗原展示在 OMV 表面，然后通过包含标签/捕获蛋白对的 Plug-and-Display 系统简化抗原展示过程。用不同蛋白捕获物修饰的 OMVs 可以同时展示多种不同的肿瘤抗原，引发协同的抗肿瘤免疫反应。此外，负载不同肿瘤抗原的生物工程化 OMVs 可以消除肺黑色素瘤转移并抑制皮下结直肠癌的生长。生物工程化的基于 OMV 的平台能够快速和同时展示抗原的能力可能有助于这些个体化肿瘤疫苗的开发。
