Table 2. Clinical trials and retrospective studies or meta-analysis in immunotherapy treatments of HCC.
| Immune-therapy strategies | Trial/study | Design | Results | Ref. |
|---|---|---|---|---|
| Adoptive immunotherapy | Randomized phase II | Adjuvant 6 versus 3 courses of CIK cell infusion immunotherapy in resected patients |
1-, 3-, 5-y - DFS rates 6 courses CIK infusion: 84.7%, 30.5%, 19.4% 3 courses CIK infusion: 83.1%, 31.7%, 23.3% |
39 |
| Retrospective analysis | Adjuvant CIK cell infusion immunotherapy in resected patients | 1, 2, 3, 4, 5-y OS rates Untreated group: 84%, 69.2%, 61.6%, 56.9%, 50.2 % CIK cells group: 93.6%, 83.3%, 76.6%, 71.1%, 65.9% |
40 | |
| Retrospective analysis | Adjuvant autologous CIK cell infusion immunotherapy versus control after locoregional procedures | Overall RRs: 79.8% versus 76.5% OS: 56 months versus 31 months PFS: 17 months versus 10 months |
41 | |
| Phase III | Adjuvant activated CIK cells infusion immunotherapy versus control in resected patients or after RFA or after percutaneous ethanol injection | mDFS: 44 months versus 30 months | 42 | |
| Meta-analysis including 13 phase II/III trials | Adjuvant activated CIK cells infusion immunotherapy after RFA and/or TACE |
1-y OS - OR=0.25 (95% CI, p < 0.001) 2-y OS - OR=0.17 (95% CI, p < 0.001) |
43 | |
| Indirect immunological strategies | Randomized phase II | TACE plus IFN-α versus TACE in unresectable HCC | mOS: 29 months versus 26 months (p = 0.003) mDFS: 23.6 months versus 20.3 months (p = 0.027) |
51 |
| Phase II | Combined intrarterial 5-FU plus PEG-IFN α-2b in advanced HCC with portal venous invasion | ORR: 73% mOS: 29.9 months |
52 | |
| Meta-analysis of 10 trials | Adjuvant IFN versus placebo | Recurrence rate - OR: 0.42 (CI 95%; p < 0.00001) | 53 | |
| Phase I | Tremelimumab in advanced HCC | Good toxicity profile PR: 17.6% SD: 45% |
58 | |
| Phase I/II | Nivolumab in advanced HCC | Good toxicity profile ORR: 20% Median duration of response: 9.9 months |
62 | |
| Phase I | Pulsed DCs by autologous cells from tumor lysate in advanced HCC | Positive feasibility Low toxicity profile |
70 | |
| Phase II | DCs pulsed with HepG2 cell lysate in advanced HCC | DCR:28% Low toxicity profile |
71 | |
| Phase I | AFP-derived vaccine in advanced HCC | T-cell increased activity in all patients | 74 | |
| Phase I | GPC3 vaccine advanced HCC |
mOS: 12.2 months in high T-cell expressing patients mOS: 8.5 months in low expressing patients |
75 | |
| Phase II | Telomerase peptide GV1001 vaccine in advanced HCC | Low toxicity profile 6 mo SD: 45.9% mTTP: 57 days |
78 | |
| Phase II | Second line therapy with lenalidomide | OS: 7.6 months PR: 15% |
||
| Indirect non immunological strategies | Phase II | Metronomic capecitabine in previously untreated and resistant to/intolerant of sorafenib advanced HCC | mPFS (untreated): 6 months mPFS (second line): 14.4 months |
89 |
| Randomized phase II | Two doses of JX-594 (high versus low dose) vaccinia virus in advanced HCC | Positive feasibility mOS: 14.1 versus 6.7 months |
90 |
Abbreviation - CI: confidence interval; CIK: cytokine induced killer; DC: dendritic cell; DCR: disease control rate; DFS: disease free survival; HCC: hepatocellular carcinoma; IFN: interferon; mDFS: median disease free survival; mOS: median overall survival; mTTP: median time to progression; ORR: overall response rate; OS: overall survival; PFS: progression free survival; PR: partial response; RFA: radiofrequency ablation; RR: recurrence rate; SD: stable disease; TACE: transarterial chemoembolization.