Engineered porous/hollow Burkholderia pseudomallei loading tumor lysate as a vaccine
Engineered porous/hollow Burkholderia pseudomallei loading tumor lysate as a vaccine
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工程化多孔/空心鼻疽伯克霍尔德氏菌负载肿瘤裂解物作为疫苗
DOI：
10.1016/j.biomaterials.2021.121141
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发表时间：
2021-09-24
期刊：
影响因子：
14
通讯作者：
Tan, Guang-Hong
中科院分区：
文献类型：
--
作者：
Huang, Feng-Ying;Dai, Shu-Zhen;Tan, Guang-Hong
由于类鼻疽伯克霍尔德菌的大小、形状和病原体相关分子模式和侵袭辅助粘附蛋白的固有表达，其可以容易地附着于树突状细胞（DC），然后被DC内化，如果修饰为载体，则导致更有效的抗原交叉呈递。本文中，我们将类鼻疽伯克霍尔德氏菌改造为用于装载肿瘤裂解物（L）和佐剂CpG（C）的多孔/中空载体（SB），以用作肿瘤疫苗（SB-LC）。我们发现类鼻疽伯克霍尔德菌的粘附蛋白促进DC对SB-LC疫苗的内化，并导致增强的DC成熟和抗原交叉表达。SB-LC诱导强大的细胞和体液抗肿瘤反应，在几种肿瘤模型中协同抑制肿瘤生长，副作用最小。此外，SB-LC疫苗接种逆转了免疫抑制性肿瘤微环境，这显然是CD 8+诱导的肿瘤铁凋亡的结果。因此，SB-LC是一种潜在的模型肿瘤疫苗，可转化为临床上可行的治疗选择。
Due to its size, shape, and inherent expression of pathogen-associated molecular patterns and invasion-assistant adhesion proteins, Burkholderia pseudomallei can easily attach to, and then be internalized by, dendritic cells (DCs), leading to more efficient antigen cross-presentation if modified as carrier. Herein, we engineered Burkholderia pseudomallei as a porous/hollow carrier (SB) for loading tumor lysates (L) and adjuvant CpG (C) to be used as a tumor vaccine (SB-LC). We found that the adhesion proteins of Burkholderia pseudomallei promote internalization of the SB-LC vaccine by DCs, and result in enhanced DC maturation and antigen crosspresentation. SB-LC induces robust cellular and humoral antitumor responses that synergistically inhibit tumor growth with minimal adverse side effects in several tumor models. Moreover, SB-LC vaccination reverses the immunosuppressive tumor microenvironment, apparently as a result of CD8+-induced tumor ferroptosis. Thus, SB-LC is a potential model tumor vaccine for translating into a clinically viable treatment option.