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Therapeutic nanovaccines sensitize EBV-associated tumors to checkpoint blockade therapy.

治疗性纳米疫苗使 EBV 相关肿瘤对检查点阻断治疗敏感。

  • 影响因子:9.85
  • DOI:10.1016/j.biomaterials.2020.120158
  • 作者列表:"Liu H","Chen H","Liu Z","Le Z","Nie T","Qiao D","Su Y","Mai H","Chen Y","Liu L
  • 发表时间:2020-06-06
Abstract

:For successful treatment of EBV-associated tumors immune tolerance must be broken. While most studies of EBV-associated tumor vaccines have focused on augmenting tumor-specific effector T cells, the effects of these vaccines on the immune-suppressive tumor microenvironment have not been investigated. Here, we describe the manufacture of a nanovaccine using tannic acid (TA) and a newly constructed protein antigen for EBV-associated tumors with interferon-α (IFN-α) or CpG as adjuvants. TA as a biocompatible material from plant self-assembles with antigens and adjuvants via hydrogen bonding to form well-defined nanoparticulate vaccines by flash nanocomplexation, a scalable yet controllable technique. By targeting lymph nodes, the nanovaccine co-loaded with CpG adjuvant induces strong immune activation and exhibits efficient inhibition tumorigenesis. Moreover, the nanovaccine combining with anti-PD-L1 results a marked decrease in tumor size and prolonged survival of tumor-bearing mice by decreasing infiltration of regulatory T cells to the tumor lesion. This suggests that the nanovaccine can reverse immune checkpoint inhibitor resistance by remodeling the tumor microenvironment. Thus, this study shows a promising strategy for treatment of EBV-positive tumors in patients.

摘要

: 为了成功治疗 EBV 相关肿瘤,必须打破免疫耐受。虽然大多数 EBV 相关肿瘤疫苗的研究都集中在增强肿瘤特异性效应 T 细胞,但这些疫苗对免疫抑制性肿瘤微环境的影响尚未得到研究。在这里,我们描述了使用单宁酸 (TA) 和一种新构建的用于 EBV 相关肿瘤的蛋白抗原,以干扰素-α (IFN-α) 或 CpG 作为佐剂的纳米疫苗的制造。TA 作为一种生物相容性材料,来自植物通过氢键与抗原和佐剂自组装,通过 flash 纳米络合形成明确的纳米疫苗,这是一种可扩展但可控的技术。通过靶向淋巴结,与 CpG 佐剂共负载的纳米疫苗诱导强烈的免疫激活,并表现出有效的抑制肿瘤发生。此外,纳米疫苗联合 anti-PD-L1 通过减少调节性 T 细胞对肿瘤病灶的浸润,使肿瘤体积明显减小,荷瘤小鼠的生存期延长。这表明纳米疫苗可以通过重塑肿瘤微环境来逆转免疫检查点抑制剂的抵抗。因此,这项研究显示了一个有前途的策略,用于治疗 EBV 阳性肿瘤的患者。

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