Surface‐Engineering of Red Blood Cells as Artificial Antigen Presenting Cells Promising for Cancer Immunotherapy,Small

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Surface‐Engineering of Red Blood Cells as Artificial Antigen Presenting Cells Promising for Cancer Immunotherapy
Small ( IF 13.0 ) Pub Date : 2017-09-01 , DOI: 10.1002/smll.201701864
Xiaoqi Sun ₁ , Xiao Han ₁ , Ligeng Xu ₁ , Min Gao ₁ , Jun Xu ₁ , Rong Yang ₁ , Zhuang Liu ₁

Affiliation

The development of artificial antigen presenting cells (aAPCs) to mimic the functions of APCs such as dendritic cells (DCs) to stimulate T cells and induce antitumor immune responses has attracted substantial interests in cancer immunotherapy. In this work, a unique red blood cell (RBC)‐based aAPC system is designed by engineering antigen peptide‐loaded major histocompatibility complex‐I and CD28 activation antibody on RBC surface, which are further tethered with interleukin‐2 (IL2) as a proliferation and differentiation signal. Such RBC‐based aAPC‐IL2 (R‐aAPC‐IL2) can not only provide a flexible cell surface with appropriate biophysical parameters, but also mimic the cytokine paracrine delivery. Similar to the functions of matured DCs, the R‐aAPC‐IL2 cells can facilitate the proliferation of antigen‐specific CD8+ T cells and increase the secretion of inflammatory cytokines. As a proof‐of‐concept, we treated splenocytes from C57 mice with R‐aAPC‐IL2 and discovered those splenocytes induced significant cancer‐cell‐specific lysis, implying that the R‐aAPC‐IL2 were able to re‐educate T cells and induce adoptive immune response. This work thus presents a novel RBC‐based aAPC system which can mimic the functions of antigen presenting DCs to activate T cells, promising for applications in adoptive T cell transfer or even in direct activation of circulating T cells for cancer immunotherapy.

中文翻译：

红细胞的表面工程作为有望用于癌症免疫治疗的人工抗原呈递细胞

模仿树突状细胞（DC）等APC功能以刺激T细胞并诱导抗肿瘤免疫反应的人工抗原呈递细胞（aAPC）的发展引起了癌症免疫治疗的广泛兴趣。在这项工作中，通过在RBC表面上工程化抗原肽加载的主要组织相容性复合体I和CD28激活抗体来设计基于独特的红细胞（aRPC）的aAPC系统，然后将其与白介素2（IL2）进一步捆绑在一起。增殖分化信号。这种基于RBC的aAPC-IL2（R-aAPC-IL2）不仅可以提供具有适当生物物理参数的柔性细胞表面，而且可以模拟细胞因子旁分泌的传递。与成熟的DC的功能类似，R‐aAPC‐IL2细胞可以促进抗原特异性CD8 + T细胞的增殖并增加炎性细胞因子的分泌。作为概念验证，我们用R-aAPC-IL2处理了C57小鼠的脾细胞，并发现这些脾细胞诱导了重要的癌细胞特异性裂解，这暗示R-aAPC-IL2能够重新培养T细胞和诱导过继性免疫反应。因此，这项工作提出了一种新颖的基于RBC的aAPC系统，该系统可以模拟抗原呈递DC激活T细胞的功能，有望用于过继T细胞转移，甚至直接激活循环T细胞以用于癌症免疫治疗。暗示R-aAPC-IL2能够重新教育T细胞并诱导过继性免疫反应。因此，这项工作提出了一种新颖的基于RBC的aAPC系统，该系统可以模拟抗原呈递DC激活T细胞的功能，有望用于过继T细胞转移，甚至直接激活循环T细胞以用于癌症免疫治疗。暗示R-aAPC-IL2能够重新教育T细胞并诱导过继性免疫反应。因此，这项工作提出了一种新颖的基于RBC的aAPC系统，该系统可以模拟抗原呈递DC激活T细胞的功能，有望用于过继T细胞转移，甚至直接激活循环T细胞以用于癌症免疫治疗。

更新日期：2017-09-01

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