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Engineered porous/hollow Burkholderia pseudomallei loading tumor lysate as a vaccine
Biomaterials ( IF 14.0 ) Pub Date : 2021-09-21 , DOI: 10.1016/j.biomaterials.2021.121141
Feng-Ying Huang 1 , Shu-Zhen Dai 1 , Jin-Yan Wang 1 , Ying-Ying Lin 1 , Cai-Chun Wang 2 , Wu-Ping Zheng 1 , Guang-Hong Tan 1
Affiliation  

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.



中文翻译:

工程多孔/空心伯克霍尔德氏菌负载肿瘤裂解物作为疫苗

由于其大小、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假鼻疽伯克霍尔德菌可以很容易地附着在树突细胞 (DC) 上,然后被树突细胞 (DC) 内化,从而导致更有效的抗原交叉呈递如果修改为载体。在此,我们将假鼻疽伯克霍尔德菌设计为多孔/中空载体 (SB),用于装载肿瘤裂解物 (L) 和佐剂 CpG (C),用作肿瘤疫苗 (SB-LC)。我们发现假鼻疽伯克霍尔德菌的粘附蛋白促进内化SB-LC 疫苗被 DC 降解,并导致 DC 成熟和抗原交叉呈递增强。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且副作用最小。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 CD8 +诱导的肿瘤铁死亡的结果。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方案。

更新日期:2021-09-24
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