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Front. Med.    2019, Vol. 13 Issue (1) : 3-11    https://doi.org/10.1007/s11684-019-0684-x
REVIEW
Adoptive cell transfer therapy for hepatocellular carcinoma
Renyu Zhang, Zhao Zhang, Zekun Liu, Ding Wei, Xiaodong Wu, Huijie Bian(), Zhinan Chen()
Department of Cell Biology, National Translational Science Center for Molecular Medicine, State Key Laboratory of Cancer Biology, Fourth Military Medical University, Xi’an 710032, China
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Abstract

Hepatocellular carcinoma (HCC) is one of the most common cancers worldwide. This malignancy is associated with poor prognosis and high mortality. Novel approaches for prolonging the overall survival of patients with advanced HCC are urgently needed. The antitumor activities of adoptive cell transfer therapy (ACT), such as strategies based on tumor-infiltrating lymphocytes and cytokine-induced killer cells, are more effective than those of traditional strategies. Currently, chimeric antigen receptor T-cell (CAR-T) immunotherapy has achieved numerous breakthroughs in the treatment of hematological malignancies, including relapsed or refractory lymphoblastic leukemia and refractory large B-cell lymphoma. Nevertheless, this approach only provides a modest benefit in the treatment of solid tumors. The clinical results of CAR-T immunotherapy for HCC that could be obtained at present are limited. Some published studies have demonstrated that CAR-T could inhibit tumor growth and cause severe side effects. In this review, we summarized the current application of ACT, the challenges encountered by CAR-T technology in HCC treatment, and some possible strategies for the future direction of immunotherapeutic research.
Keywords adoptive cell transfer therapy      hepatocellular carcinoma      T cell      chimeric antigen receptor      immunotherapy     
Corresponding Author(s): Huijie Bian,Zhinan Chen   
Just Accepted Date: 29 December 2018   Online First Date: 18 January 2019    Issue Date: 12 March 2019
 Cite this article:   
Renyu Zhang,Zhao Zhang,Zekun Liu, et al. Adoptive cell transfer therapy for hepatocellular carcinoma[J]. Front. Med., 2019, 13(1): 3-11.
 URL:  
https://academic.hep.com.cn/fmd/EN/10.1007/s11684-019-0684-x
https://academic.hep.com.cn/fmd/EN/Y2019/V13/I1/3
Cells used for ACT Patients (n) total Patients (n) treated with ACT Overall survival
(ACT vs. Control or ACT alone)		 Recurrence rate (ACT vs. Control or ACT alone) Study reference
Tumor-infiltrating lymphocytes 15 15 100% (14 months) 20% (14 months) [23]
Tumor-infiltrating lymphocytes 150 76 68% vs. 62% (5 years) 59% vs. 77% (4.4 years) [24]
Cytokine-induced killer cells 132 66 42.4% vs. 24.2%(3 years) − [25]
Cytokine-induced killer cells 127 41/43 37.9%/38.1% vs. 36.9% (5 years) 73%/72% vs. 76% (5 years) [26]
Cytokine-induced killer cells 230 115 − 39.5% vs. 49.1% (4.4 years) [27]
Cytokine-induced killer cells 85 45 100% vs. 100% (18 months) 15.6% vs. 40.0% (18 months) [28]
Cytokine-induced killer cells 83 42 − 7.14% vs. 23.1% (1 year) [29]
Cytokine-induced killer cells 146 72 62.4% vs. 18.8% (2 years) − [30]
Tab.1  Summary of clinical trials on the applicability of TIL and CIK as HCC treatment strategies
Clinical trial identifier Antigen Phase Estimated enrollment Infusion Doses Sponsor Status
NCT02715362 GPC3 I/II 30 Transcatheter arterial infusion (1–10) × 106/kg Shanghai GeneChem Co., Ltd. Recruiting
NCT03130712 GPC3 I/II 10 Intratumor injection (1–10) × 106 Shanghai GeneChem Co., Ltd. Recruiting
NCT03198546 GPC3 I 30 − − Second Affiliated Hospital of Guangzhou Medical University Recruiting
NCT03146234 GPC3 − 20 Intravenous injection Self-controlled dose escalation Renji Hospital Recruiting
NCT03349255 AFP I 18 Intravenous infusion and intrahepatic artery infusion − Aeon Therapeutics (Shanghai) Co., Ltd. Recruiting
NCT02587689 MUC1 I/II 20 − − PersonGen BioTherapeutics (Suzhou) Co., Ltd. Recruiting
NCT02959151 GPC3 I/II 20 Vascular interventional therapy or intratumor injection (1.25–4) × 107/cm3 tumor bulk Shanghai GeneChem Co., Ltd. Recruiting
NCT03013712 EpCAM I/II 60 Vascular interventional mediated or endoscopy infusion (1–10) × 106/kg First Affiliated Hospital of Chengdu Medical College Recruiting
NCT02905188 GPC3 I 14 − 1 × 107/m2
3 × 107/m2
1 × 108/m2
3 × 108/m2
1 × 109/m2		 Baylor College of Medicine Not yet recruiting
NCT03084380 GPC3 I/II 20 Transcatheter arterial chemoembolization combined with CAR-T infusion − Xinqiao Hospital of Chongqing Not yet recruiting
NCT03302403 GPC3 − 48 Intravenous injection Self-controlled dose escalation First Affiliated Hospital of Wenzhou Medical University Not yet recruiting
NCT02723942 GPC3 I/II 60 − − Fuda Cancer Hospital, Guangzhou Completed
NCT02395250 GPC3 I 13 − − Renji Hospital Terminated
Tab.2  Summary of clinical trials on the applicability of CAR-T therapy as a HCC treatment strategy
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