Zhao Qiang, Huang Jinbo, Luo Weixin, Tan Haidong, Wong Regina Wan Ju, Liu Zhiying, Qin Meiting, Li Jiahao, Koh Sarene, Wai Lu-En, Wang Tingting, Dan Jia, Guo Zhiyong, He Xiaoshun
Organ Transplant Center, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China.
Guangdong Provincial Key Laboratory of Organ Donation and Transplant Immunology, Guangzhou, China.
Clin Cancer Res. 2025 Sep 15;31(18):3886-3896. doi: 10.1158/1078-0432.CCR-25-1245.
This study aimed to preliminarily evaluate the safety, tolerability, and antitumor efficacy of hepatitis B virus (HBV)-specific T-cell receptor (TCR)-T cell therapy combining mRNA electroporation and lentiviral transduction in patients with recurrent HBV-hepatocellular carcinoma after liver transplantation.
In this pilot study (NCT04677088), two types of autologous HBV-specific TCR-redirected T cells were assessed without prior lymphodepletion: (i) multiple infusions of mRNA-electroporated HBV-TCR-T cells (mRNA-HBV-TCR-T cells) and (ii) one to three infusions of lentiviral-transduced HBV-TCR-T cells (lenti-HBV-TCR-T cells). Treatment-related adverse events were assessed using the Common Terminology Criteria for Adverse Events, and antitumor efficacy was evaluated using CT imaging according to RECIST v1.1 criteria. Progression-free survival (PFS) was defined as the time from the start of study treatment until objective tumor progression or death.
Both mRNA-electroporated and lentiviral-transduced HBV-specific TCR-T cells demonstrated a favorable safety profile, with only grade 1 to 2 treatment-related adverse events observed. In the mRNA-HBV-TCR-T cells cohort, the median PFS was 2.32 months (range, 1.87-2.77 months). The combination therapy cohort (mRNA-HBV-TCR-T cells + lenti-HBV-TCR-T cells) showed a median PFS of 7.34 months (range, 4.47-7.60 months). CT imaging indicated effective tumor control in the combination therapy group.
This study preliminarily suggests that the combination of mRNA-HBV-TCR-T cells and lenti-HBV-TCR-T cells could be a safe and potentially effective approach for treating patients following liver transplantation in the context of lifelong immunosuppression drug administration. Further studies are needed to refine treatment strategies and assess long-term safety and efficacy in this special patient population.
本研究旨在初步评估在肝移植术后复发的乙型肝炎病毒（HBV）相关肝细胞癌患者中，结合mRNA电穿孔和慢病毒转导的HBV特异性T细胞受体（TCR）-T细胞疗法的安全性、耐受性和抗肿瘤疗效。
在本前瞻性研究（NCT04677088）中，在未进行预先淋巴细胞清除的情况下评估了两种类型的自体HBV特异性TCR重定向T细胞：（i）多次输注经mRNA电穿孔的HBV-TCR-T细胞（mRNA-HBV-TCR-T细胞）和（ii）一至三次输注经慢病毒转导的HBV-TCR-T细胞（慢病毒-HBV-TCR-T细胞）。使用不良事件通用术语标准评估治疗相关不良事件，并根据RECIST v1.1标准使用CT成像评估抗肿瘤疗效。无进展生存期（PFS）定义为从研究治疗开始至客观肿瘤进展或死亡的时间。
经mRNA电穿孔和慢病毒转导的HBV特异性TCR-T细胞均显示出良好的安全性，仅观察到1至2级治疗相关不良事件。在mRNA-HBV-TCR-T细胞队列中，中位PFS为2.32个月（范围1.87 - 2.77个月）。联合治疗队列（mRNA-HBV-TCR-T细胞 + 慢病毒-HBV-TCR-T细胞）的中位PFS为7.34个月（范围4.47 - 7.60个月）。CT成像表明联合治疗组肿瘤得到有效控制。
本研究初步表明，在终身使用免疫抑制药物的情况下，mRNA-HBV-TCR-T细胞与慢病毒-HBV-TCR-T细胞联合使用可能是治疗肝移植患者的一种安全且潜在有效的方法。需要进一步研究以优化治疗策略并评估该特殊患者群体的长期安全性和疗效。
