Targets of immunotherapy for hepatocellular carcinoma: An update

Table 1 Immune checkpoint inhibitor therapy for hepatocellular carcinoma

Immune checkpoint inhibitor therapy
Agent	Type of study	Study details	Outcome
Tremelimumab (anti-CTLA4)[45]	Phase II clinical trial	21 HCC patients infected with hepatitis C virus and not eligible for surgery or locoregional therapy 15 mg/kg IV every 90 d	17.6% patients-partial response; 58.8% patients-stable disease; Time to progression-6.48 mo; Overall survival-8.2 mo; Decreased viral load
TRC105 (carotuximab) antibody to CD105[46]	Phase I/II study	TRC105 (15 mg/kg) every 2 wk given with sorafenib 400 mg twice daily	Tumor ablation utilizing RFA and TACE enhance the efficacy of tremelimumab; Improves intratumoral effector CD8+ T cells infiltration
Nivolumab (anti-PD-1)[47]	CheckMate 040 phase I/II dose-escalation study	182 patients with advanced HCC; Patients naive to or previously treated with sorafenib received 0.1-10 mg/kg and 3 mg/kg once every 2 wk	Durable responses with long-term survival and favorable safety in both sorafenib-naive and -experienced patients; 3.8% complete response, 14.8% partial response, and 62.6% disease control rate
Nivolumab (anti-PD-1)[33]	Phase I/II study NCT01658878	262 HCC patients; HCC patients on sorafenib	1.4% complete response; 18.2% partial response; 83% overall survival at 6 mo
Pembrolizumab (anti-PD-1)[48]	KEYNOTE-224 trial	104 advanced HCC patients on sorafenib	1% complete response; 16% partial response; 54% overall survival at 12 mo
Durvalumab (PD-L1) and tremelimumab (CTLA4)[49]	Phase I/II, open-label, randomized study	For the efficacy of durvalumab combined with tremelimumab in unresectable HCC	No unexpected safety signals with durvalumab and tremelimumab seen in unresectable HCC patients
Tremelimumab (CTLA4)[50]	Phase II trial NCT01853618	32 patients with HCC with HCV; Tremelimumab at 3.5 and 10 mg/kg i.v. every 4 wk for 6 doses, followed by 3-monthly infusions; Combined with subtotal radiofrequency ablation or chemoablation at day 36	No dose-limiting toxicities; Accumulation of intratumoral CD8+ T cells; 26% partial response

CTLA-4: Cytotoxic T lymphocyte protein 4; PD-1: Programmed cell death protein 1; HCC: Hepatocellular carcinoma; HCV: Hepatitis C virus; RFA: Radiofrequency ablation; TACE: Transarterial chemoembolization.