A vaccine for photodynamic immunogenic cell death: tumor cell caged by cellular disulfide-thiol exchange for immunotherapy.
A vaccine for photodynamic immunogenic cell death: tumor cell caged by cellular disulfide-thiol exchange for immunotherapy.
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DOI：
10.1039/d0bm01393e
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发表时间：
2020-12
影响因子：
6.6
通讯作者：
Ya Wen;Yiqiong Liu;Fangfang Guo;Yi Han;Qiansai Qiu;Yan Li;Haiqing Dong;T. Ren;Yongyong Li-Yongyong-L
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文献类型：
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作者：
Ya Wen;Yiqiong Liu;Fangfang Guo;Yi Han;Qiansai Qiu;Yan Li;Haiqing Dong;T. Ren;Yongyong Li-Yongyong-L
免疫原性细胞死亡（ICD）具有治疗潜力，但其抗癌免疫受到肿瘤区域内原位免疫抑制微环境（如抗原呈递细胞功能障碍）的极大阻碍。在此，我们提出了一种体外ICD诱导模式，以规避这种免疫激活的损害。为此，一个“热”，即，免疫原性的全肿瘤细胞疫苗在体外产生，并在正常组织中皮下接种，远离原位免疫抑制肿瘤区域的部位，以充分利用ICD诱导的抗肿瘤免疫。特别是，免疫原性垂死的肿瘤细胞，笼细胞二硫-硫醇交换，光活化介导的。在皮下接种后，光活化的笼状活细胞疫苗（CLCV）发挥多持久的免疫刺激特性，当其被CpG佐剂化时，有效地促进树突状细胞（DC）活化并在体内激发稳健的CD 8 + T细胞应答。重要的是，所产生的T细胞应答显示出保护75%用CLCV预免疫的小鼠免受肿瘤引发，并在治疗环境中显著延缓肿瘤生长。本文提出的策略可能有助于丰富目前用于癌症免疫治疗的疫苗设计。
It has been suggested that immunogenic cell death (ICD) has therapeutic potential; however, its anticancer immunity is considerably hampered by the in situ immunosuppressive microenvironment within the tumor area, such as the dysfunction of antigen-presenting cells. Herein, we present an in vitro ICD-inducing modality to circumvent such impairment of immune activation. To this end, a "hot", i.e., immunogenic, whole tumor cell vaccine is generated in vitro and subcutaneously vaccinated in the normal tissue, departing from the site of the in situ immunosuppressive tumor area, to fully leverage the ICD-inducing antitumor immunity. In particular, the immunogenic dying tumor cells, caged by cellular disulfide-thiol exchange, are mediated by photoactivation. After subcutaneous vaccination, the photoactivated caged live cell vaccine (CLCV) exerts multi-durable immunostimulatory property, which, when adjuvanted by CpG, efficiently promotes dendritic cell (DC) activation and elicits robust CD8+ T-cell responses in vivo. Importantly, the generated T-cell responses are shown to protect 75% mice preimmunized with CLCV against tumor initiation and significantly retards tumor growth in the therapeutic setting. The strategy presented here may help to enrich the current vaccine design for cancer immunotherapy.