研究动态
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激光激活原位疫苗可增强癌症免疫循环。

Laser-Activatable in Situ Vaccine Enhances Cancer-Immunity Cycle.

发表日期:2023 Nov 11
作者: Zhenyu Wang, Tingting You, Qianyi Su, Wenjia Deng, JiaBao Li, Saixiang Hu, Shengjun Shi, Zhaowei Zou, Jisheng Xiao, Xiaopin Duan
来源: Cell Death & Disease

摘要:

癌症中的免疫反应反映了一系列精心调控的事件;然而,当前的肿瘤免疫疗法通常针对增强抗肿瘤免疫力的一个关键方面。在本研究中,我们开发了一种基于纳米平台(Fe3O4@IR820@CpG)的免疫治疗策略,该策略针对癌症免疫周期中的多个关键步骤:1)促进肿瘤衍生蛋白(TDP)的释放,包括肿瘤-相关抗原和促免疫刺激因子),除了直接杀伤作用外,还通过光热疗法(PTT)和光动力疗法(PDT); 2) 捕获释放的 TDP 并将其与 CpG(Toll 样受体 9 [TLR-9] 激动剂)一起递送至抗原呈递细胞 (APC),以促进抗原呈递和 T 细胞激活; 3)与抗程序性死亡配体1抗体(α-PD-L1)结合,增强T细胞的杀伤肿瘤能力,共同提升了我们对结直肠癌、肝癌和乳腺癌的卓越抗肿瘤效果。 Fe3 O4 @IR820@CpG 与 α-PD-L1 的广谱抗肿瘤活性表明,优化地控制抗癌免疫不是单独的,而是作为一个整体提供有前途的临床策略。本文受版权保护。保留所有权利。本文受版权保护。版权所有。
The immune response in cancer reflects a series of carefully regulated events; however, current tumor immunotherapies typically address a single key aspect to enhance anti-tumor immunity. In the present study, we developed a nanoplatform (Fe3 O4 @IR820@CpG)-based immunotherapy strategy that targets the multiple key steps in cancer-immunity cycle: 1) promotes the release of tumor-derived proteins (TDPs), including tumor-associated antigens and pro-immunostimulatory factors), in addition to the direct killing effect, by photothermal (PTT) and photodynamic therapy (PDT); 2) captures the released TDPs and delivers them, together with CpG (a Toll-like receptor 9 [TLR-9] agonist) to antigen presenting cells (APCs) to promote antigen presentation and T cell activation; 3) enhances the tumor-killing ability of T cells by combining with anti-programmed death ligand 1 antibody (α-PD-L1), which collectively advances our outstanding of the anti-tumor effects on colorectal, liver and breast cancers. The broad-spectrum anti-tumor activity of Fe3 O4 @IR820@CpG with α-PD-L1 demonstrated that optimally manipulating anti-cancer immunity not singly but as a group provides promising clinical strategies. This article is protected by copyright. All rights reserved.This article is protected by copyright. All rights reserved.