Cheng Jiaqing, Wu Suxin, Zhu Chenlu, Lin Shengzhe, Liu Fang, Chen Shuping, Ye Yunbin
The School of Basic Medical Sciences, Fujian Medical University, Fuzhou, Fujian, China.
Laboratory of Immuno-Oncology, Clinical Oncology School of Fujian Medical University, Fujian Cancer Hospital, Fuzhou, Fujian, China.
Front Immunol. 2025 Aug 29;16:1633345. doi: 10.3389/fimmu.2025.1633345. eCollection 2025.
Hepatocellular carcinoma (HCC) represents a significant health challenge, with immunotherapy serving as a crucial component of its complex treatment regimen. This study investigates the use of TP53Y220C as a preferred antigen to induce cytotoxic T lymphocytes (CTLs) for cytotoxic effects against HCC.
The TP53 mRNA (mTP53) was synthesized through an transcription method and subsequently introduced into dendritic cells (DCs) using bacterial outer membrane vesicles expressing L7Ae and Listeria monocytogenes lysin O (OMV-LL), electroporation, and lipid nanoparticles, respectively. Co-culture of differently treated DCs with initial T cells induces CTLs. The cytotoxic effects of CTLs on hepatocellular carcinoma were evaluated through experiments such as flow cytometry and mouse tumour models.
We assessed the therapeutic efficacy of CTLs, activated by mTP53-loaded DCs, in a murine model of HCC. Results demonstrate that CTLs, activated by DCs loaded with mTP53 via OMV-LL or electroporation, effectively initiated immune responses against HCC. While OMV-LL were less efficient than electroporation in mRNA delivery, they induced a significant pro-inflammatory response and activated the innate immune system.
This study highlights OMV-LL as an innovative mRNA delivery approach to DCs for CTLs activation and demonstrates their potential in CTLs-based therapy for HCC.
肝细胞癌（HCC）是一项重大的健康挑战，免疫疗法是其复杂治疗方案的关键组成部分。本研究调查了使用TP53Y220C作为首选抗原诱导细胞毒性T淋巴细胞（CTL）对HCC产生细胞毒性作用。
通过转录方法合成TP53信使核糖核酸（mTP53），随后分别使用表达L7Ae的细菌外膜囊泡和单核细胞增生李斯特菌溶素O（OMV-LL）、电穿孔和脂质纳米颗粒将其导入树突状细胞（DC）。将经不同处理的DC与初始T细胞共培养诱导CTL。通过流式细胞术和小鼠肿瘤模型等实验评估CTL对肝细胞癌的细胞毒性作用。
我们在HCC小鼠模型中评估了由负载mTP53的DC激活的CTL的治疗效果。结果表明，通过OMV-LL或电穿孔负载mTP53的DC激活的CTL有效地引发了针对HCC的免疫反应。虽然OMV-LL在信使核糖核酸递送方面不如电穿孔有效，但它们诱导了显著的促炎反应并激活了先天免疫系统。
本研究强调OMV-LL是一种用于激活DC以产生CTL的创新信使核糖核酸递送方法，并证明了它们在基于CTL的HCC治疗中的潜力。
