Department of Breast and Thyroid Surgery, The Second Affiliated Hospital of Hainan Medical University, Key Laborato1y of Tropical Translational Medicine of Ministry of Education & Hainan Provincial Key Laboratory of Tropical Medicine, Haikou, 570311, China.
Department of Respiratory Diseases, The First Affiliated Hospital of Hainan Medical University, Haikou, 570102, China.
Biomaterials. 2021 Nov;278:121141. doi: 10.1016/j.biomaterials.2021.121141. Epub 2021 Sep 21.
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 cross-presentation. 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.
由于其大小、形状以及固有表达的病原体相关分子模式和侵袭辅助黏附蛋白，伯克霍尔德菌假单胞菌可以很容易地附着在树突状细胞（DCs）上，然后被内吞，如果经过修饰作为载体，会导致更有效的抗原交叉呈递。在这里，我们将伯克霍尔德菌假单胞菌设计为多孔/空心载体（SB），用于装载肿瘤裂解物（L）和佐剂 CpG（C），用作肿瘤疫苗（SB-LC）。我们发现，伯克霍尔德菌假单胞菌的黏附蛋白促进了 DC 对 SB-LC 疫苗的内吞作用，导致 DC 成熟和抗原交叉呈递增强。SB-LC 诱导强烈的细胞和体液抗肿瘤反应，与几种肿瘤模型中的最小不良反应协同抑制肿瘤生长。此外，SB-LC 疫苗接种逆转了免疫抑制性肿瘤微环境，这显然是由于 CD8 诱导的肿瘤铁死亡。因此，SB-LC 是一种有潜力的模型肿瘤疫苗，可以转化为一种可行的临床治疗选择。
