Chen Weiguo, Sheng Ping, Chen Yujiang, Liang Yi, Wu Sixin, Jia Liying, He Xin, Zhang Chun-Feng, Wang Chong-Zhi, Yuan Chun-Su
School of Traditional Chinese Pharmacy, China Pharmaceutical University, Nanjing, 210009, China.
School of Biomedical Sciences, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong SAR, China.
Chem Eng J. 2023 Jan;451(Pt 2). doi: 10.1016/j.cej.2022.138781. Epub 2022 Aug 24.
Inducing cell death while simultaneously enhancing antitumor immune responses is a promising therapeutic approach for multiple cancers. Celastrol (Cel) and 7-ethyl-10-hydroxycamptothecin (SN38) have contrasting physicochemical properties, but strong synergy in immunogenic cell death induction and anticancer activity. Herein, a hypoxia-sensitive nanosystem (CS@TAP) was designed to demonstrate effective immunotherapy for colorectal cancer by systemic delivery of an immunostimulatory chemotherapy combination. Furthermore, the combination of CS@TAP with anti-PD-L1 mAb (αPD-L1) exhibited a significant therapeutic benefit of delaying tumor growth and increased local doses of immunogenic signaling and T-cell infiltration, ultimately extending survival. We conclude that CS@TAP is an effective inducer of immunogenic cell death (ICD) in cancer immunotherapy. Therefore, this study provides an encouraging strategy to synergistically induce immunogenic cell death to enhance tumor cytotoxic T lymphocytes (CTLs) infiltration for anticancer immunotherapy.
在诱导细胞死亡的同时增强抗肿瘤免疫反应，是一种针对多种癌症颇具前景的治疗方法。雷公藤红素（Cel）和7-乙基-10-羟基喜树碱（SN38）具有截然不同的物理化学性质，但在诱导免疫原性细胞死亡和抗癌活性方面具有强大的协同作用。在此，设计了一种对缺氧敏感的纳米系统（CS@TAP），通过全身递送免疫刺激化疗组合，来证明其对结直肠癌的有效免疫治疗效果。此外，CS@TAP与抗PD-L1单克隆抗体（αPD-L1）联合使用时，显示出显著的治疗效果，可延缓肿瘤生长，并增加免疫原性信号的局部剂量和T细胞浸润，最终延长生存期。我们得出结论，CS@TAP是癌症免疫治疗中免疫原性细胞死亡（ICD）的有效诱导剂。因此，本研究提供了一种令人鼓舞的策略，可协同诱导免疫原性细胞死亡，以增强肿瘤细胞毒性T淋巴细胞（CTLs）浸润，用于抗癌免疫治疗。
