Targets of immunotherapy for hepatocellular carcinoma: An update

Table 4 Clinical trials on adoptive cell transfer therapy

Clinical trials #	Phase	Aim and design	Status
NCT03563170	Phase 1b/2	Combining innate high-affinity natural killer (hank) cell therapy with adenoviral and yeast-based vaccines to induce t-cell responses vs sorafenib	Withdrawn
NCT03008343	Phase I/II	Combination of IRE and NK cells immunotherapy vs IRE alone	Completed, no result posted
NCT01147380	Phase I	Natural killer cell therapy for hepatoma liver transplantation (MIAMINK); To evaluate feasibility and safety of the adoptive transfer of activated NK cells	Completed; No adverse events reported
NCT02008929	Phase II	To evaluate the safety and efficacy of injecting MG4101 (ex vivo expanded allogeneic NK cell) as a secondary treatment after curative liver resection in advanced HCC	Completed; No study results posted
NCT01749865	Phase III	CIK treatment in 200 patients with HCC who underwent radical resection	Completed; No study results posted
NCT02723942	Phase I/II	To evaluate the safety and efficacy of CAR-T cell immunotherapy for GPC3 positive hepatocellular carcinoma	Withdrawn due to revision of local regulations
NCT03198546	Phase I	GPC3 and/or TGF-β targeting CAR-T cells in	Recruiting
NCT03130712	Phase I/II	GPC3-targeted T cells by intratumor injection for advanced HCC (GPC3-CART)	Unknown
NCT02715362	Phase I/II	GPC3 redirected autologous t cells for advanced HCC (GPC3-CART)	Unknown
NCT03013712	Phase I/II	GPC3-targeted T cells by intratumor injection for advanced HCC (GPC3-CART)	Unknown
NCT03349255	Phase I	Autologous ET1402L1-CAR T cells in AFP expressing HCC	Terminated and will study new T-cell construct
NCT02905188	Phase I	To find the biggest dose of GLYCAR T cells that is safe, to see how long they last in the body, to learn what the side effects in GPC3-positive HCC	Recruiting patients; Partial response with no toxicities
NCT03146234	Single arm, open-label pilot study	to determine the safety and efficacy of CAR-GPC3 T cells in patients with relapsed or refractory HCC following cyclophosphamide and fludarabine	Completed; Had a tolerable toxicity profile with no grade 3/4 neurotoxicity; Overall survival 9.1
NCT02395250	Phase I	To evaluate the safety and effectiveness of anti-GPC3 CAR T in patients with relapsed or refractory HCC	Completed, no result posted
NCT03980288	Phase I	4th generation chimeric antigen receptor T cells targeting glypican-3 (CAR-GPC3 T cells) in patients with advanced HCC	Recruiting patients
NCT04121273	Phase I	GPC3-targeted CAR-T cell for treating GPC3 positive advanced HCC	Recruiting patients
NCT03884751	Phase I	Clinical study of chimeric antigen receptor T cells targeting glypican-3 (CAR-GPC3 T cells) in patients with advanced HCC	Recruiting patients
NCT04093648	Phase I	T cells co-expressing a second generation glypican 3-specific chimeric antigen receptor with cytokines interleukin-21 and 15 as immunotherapy for patients with liver cancer (TEGAR)	Withdrawn (the key elements of this study were incorporated into another study)
NCT03013712	Phase I/II	CAR T cells targeting EpCAM positive cancer (CARTEPC); To evaluate the safety and efficacy of chimeric antigen receptor (CAR) T cells targeting EpCAM	Unknown

NK: Natural killer; IL: Interleukin; HCC: Hepatocellular carcinoma; CIK: Cytokine-induced killer; TIL: Tumor-infiltrating lymphocytes; RFA: Radiofrequency ablation; CAR: Chimeric antigen receptor; Adenoviral and Yeast based vaccines: ETBX-011, GI-4000, avelumab, Aldoxorubicin hydrochloride, ETBX-051, ETBX-061, GI-6207, GI-6301, and N-803; IRE: Irreversible electroporation; LDC: Lymphodepleting conditioning; GLYCAR: Glypican 3-specific chimeric antigen receptor expressing T cells for hepatocellular carcinoma; HCC: Hepatocellular carcinoma.