Ma Yuk Ting, Zuo Jianmin, Kirkham Amanda, Curbishley Stuart, Blahova Miroslava, Rowe Anna L, Bathurst Camilla, Mehrzad Homoyoon, Karkhanis Salil, Punia Pankaj, James Martin W, Stern Nick, Rao Ankit, Hull Diana, Lowe Faye, Sylla Panagiota, Webster Luke, Hussain Syed, Yap Christina, Palmer Daniel, Adams David H
Institute of Immunology and Immunotherapy, University of Birmingham, Birmingham, United Kingdom.
University Hospitals Birmingham NHS Foundation Trust, Birmingham, United Kingdom.
Clin Cancer Res. 2025 Aug 14;31(16):3412-3423. doi: 10.1158/1078-0432.CCR-25-0142.
A previous study by our group using dendritic cells (DC) pulsed ex vivo with the lysate of the HepG2 cell line showed evidence of antigen-specific T-cell responses in some patients with advanced hepatocellular carcinoma. The ImmunoTACE trial evaluated the preliminary activity of this vaccine in combination with transarterial chemoembolization (TACE) in patients with intermediate-stage hepatocellular carcinoma.
A randomized phase II trial was conducted in three tertiary referral centers in the United Kingdom. Eligible patients were randomly assigned in a 1:1 ratio to TACE + preconditioning cyclophosphamide or to TACE + preconditioning cyclophosphamide + DC infusions. The primary endpoint was progression-free survival time using RECIST v1.1 criteria. Additional endpoints included safety and immune responses.
Between March 2016 and October 2019, 55 patients were randomized, of whom 48 were evaluable (24 in each group). The median progression-free survival time using RECIST criteria was 18.6 months in patients treated with chemoembolization + preconditioning cyclophosphamide + DC infusions compared with 10.4 months in those treated with chemoembolization + preconditioning cyclophosphamide alone (HR = 0.43; upper value of one-sided 80% confidence interval, 0.57; P = 0.016). The addition of DC infusions did not significantly increase the incidence or severity of adverse events. An enhanced antigen (α-fetoprotein)-specific immune response was observed in patients treated with DC vaccination.
The addition of DC infusions to TACE and preconditioning cyclophosphamide has shown promising preliminary activity and merits further investigation in a larger randomized trial.
我们小组之前的一项研究使用经体外与HepG2细胞系裂解物脉冲处理的树突状细胞（DC），在一些晚期肝细胞癌患者中显示出抗原特异性T细胞反应的证据。免疫TACE试验评估了这种疫苗与经动脉化疗栓塞术（TACE）联合用于中期肝细胞癌患者的初步活性。
在英国的三个三级转诊中心进行了一项随机II期试验。符合条件的患者按1:1的比例随机分配接受TACE + 预处理环磷酰胺或TACE + 预处理环磷酰胺 + DC输注。主要终点是使用RECIST v1.1标准的无进展生存时间。其他终点包括安全性和免疫反应。
2016年3月至2019年10月期间，55例患者被随机分组，其中48例可评估（每组24例）。使用RECIST标准，接受化疗栓塞 + 预处理环磷酰胺 + DC输注的患者中位无进展生存时间为18.6个月，而仅接受化疗栓塞 + 预处理环磷酰胺的患者为10.4个月（HR = 0.43；单侧80%置信区间上限，0.57；P = 0.016）。添加DC输注并未显著增加不良事件的发生率或严重程度。在接受DC疫苗接种的患者中观察到增强的抗原（甲胎蛋白）特异性免疫反应。
在TACE和预处理环磷酰胺中添加DC输注已显示出有前景的初步活性，值得在更大规模的随机试验中进一步研究。
