Targets of immunotherapy for hepatocellular carcinoma: An update

Table 5 Vaccine therapy for hepatocellular carcinoma

Vaccine	Phase	Study design	Outcome
Autologous dendritic cells (DCs) generated ex vivo in the presence of GM-CSF and IL-4[70]	Phase I	10 patients with unresectable primary liver cancer	Immunization well tolerated without significant toxicity
Mature autologous DCs[71]	Phase II	To investigate the safety and efficacy of intravenous vaccination	Safe and well tolerated with evidence of antitumor efficacy
Ilixadencel (pro-inflammatory allogeneic DCs stimulated by GM-CSF and IL-4)[72]	Phase I trial	17 HCC patients; As monotherapy or in combination with sorafenib to evaluate tolerability	Increased tumor specific CD8+ T cells in peripheral blood (73%); 1 grade 3 adverse event
GPC3 peptide[67]	Open-label, phase I clinical trial	33 patients with advanced HCC; To evaluate safety of GPC3 peptide, immune response, tumor response, time to tumor progression, and overall survival	GPC3 vaccination was well-tolerated; 1 patient partial response; 19 patient stable disease; 2 mo after vaccination; Measurable immune responses and antitumor efficacy
Pexa-Vec (modified poxvirus JX-594)[73]	Randomized phase II dose-finding trial	30 patients with advanced HCC; 3 intra-tumoral injections; To determine the optimal JX-594 dose	Dose related survival benefit; Increased median survival of 14.1 mo compared to 6.7 mo
Pexa-Vec (JX-594)[74]	Phase 2, open-label, randomized dose finding study	Patients with advanced HCC; Intra-tumoral injection 3 times every 2 wk
Pexa-Vec (pexastimogene devacirepvec) followed by sorafenib[75]	Global, randomized, open-label phase III trial (PHOCUS)	459 patients will be recruited; To evaluate overall survival, time to progression, progression-free survival, overall response rate and disease control rate	Trial completed; 5% adverse events

IL: Interleukin; GM-CSF: Granulocyte-macrophage colony-stimulating factor; HCC: Hepatocellular carcinoma.