Immunotherapy for Hepatocellular Carcinoma: A 2021 Update
Abstract
Simple Summary
Abstract
1. Introduction
2. Immune Checkpoint Inhibitors in Hepatocellular Carcinoma
2.1. Nivolumab
2.2. Pembrolizumab
2.3. Atezolizumab
2.4. Tremelimumab
3. Vaccine Therapy in Hepatocellular Carcinoma
3.1. Alpha-Fetoprotein (AFP) Peptide
3.2. Glypican-3 (GPC3)
3.3. Multidrug Resistance-Associated Protein 3 (MRP3)
3.4. NY-ESO-1 and MAGE-A
3.5. Dendritic Cell Vaccine
3.6. Oncolytic Viruses
4. Adoptive Cell Transfer in Hepatocellular Carcinoma
4.1. CIK Cells
4.2. Chimeric Antigen Receptor T Cells (CAR-T)
5. Combinations Strategies of Immunotherapies
6. Hepatitis Infection and Immunotherapy
7. Predictive Biomarkers in HCC Immunotherapy
8. Conclusions
Funding
Conflicts of Interest
References
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Intervention | Cancer Stage | Clinical Phase/Identifier | Progression Free Survival (PFS) (Months, 95% CI) | Median Overall Survival (OS) (Months, 95% CI) | Response Rates (%, 95% CI) | Bibliography |
---|---|---|---|---|---|---|
Nivolumab | Advanced HCC | Phase I/II, NCT01658878 | 3.4 (1.6–6.9), for DS 4.1 (3.7–5.5), for EX | 15.0 (9.6–20.2), for DS NR, for EX | 15% (6–28), for DS 20% (15–26), for EX | [52] |
Nivolumab | Advanced HCC | Phase III, NCT02576509 | 3.7 (3.1–3.9) | 16.4 (13.9–18.4) | 15% | [53] |
Sorafenib | 3.8 (3.7–4.5) | 14.7 (11.9–17.2) (HR 0.84, p = 0.0419) | 7% | |||
Pembrolizumab, sorafenib | Advanced HCC | Phase II, NCT02702414 | 4.8 (3.4–6.6) | 12,9 (9,7–15,5) | 17% (11–26) | [54] |
Pembrolizumab | Second-line, Advanced HCC | Phase III NCT02702401 | 3.0 (2.8–4.1) | 13.9 (11.6–16.0) | 18.3 (14.0–23.4) | [55] |
placebo | 2.8 (2.5–4.1) | 10.6 (8.3–13.5) (HR 0.781, p = 0.023) | 4.4 (1.6–9.4) | |||
Pembrolizumab, Lenvatinib | Unresectable HCC | Phase Ib | 9.3 per mRECIST 8.6 per RECIST v1.1. | 22.0 | 46.0% (36.0–56.3) per mRECIST 36.0% (26.6%–46.2) per RECIST v1.1 | [56] |
Atezolizumab, Bevacizumab | Unresectable HCC | Phase Ib NCT02715531 | 5.6 (3.6–7.4) | [57] | ||
Atezolizumab | 3.4 (1.9–5.2) (HR 0.55, p = 0.0108) | |||||
Atezolizumab/Bevacizumab | Unresectable HCC | Phase III NCT03434379 | 6.8 (5.7–8.3) | 67.2% (61.3–73.1) | [58] | |
Sorafenib | 4.3 (4.0–5.6) (HR 0.59, p < 0.001) | 54.6% (45.2–64.0) 12 months response | ||||
Tremelimumab | HCC | Phase II NCT01008358 | 6.48 (3.95–9.14) | 17.6% | [59] | |
Tremelimumab, RFA or TACE | Advanced HCC | Phase I/II NCT01853618 | 7.5 (5.6–9.3) | 8.4 (6.5–10.3) | [60] |
Intervention | Cancer Stage | Clinical Phase/Identifier | Progression Free Survival (PFS) (Months, 95% CI) | Median Overall Survival (OS) (Months, 95% CI) | Response Rates (%, 95% CI) | Bibliography | |
---|---|---|---|---|---|---|---|
GPC3-vaccine | Advanced HCC | Phase I, UMIN000001395 | 3.4 (2.1–4.6) | 9.0 (8.0–10.0) | 91% | [93] | |
GPC3-vaccine, Surgery and RFA | Adjuvant therapy | Phase II | 20.1 (14.7–25.5) | 1 year at 24%, 2 years at 52.4% | [94] | ||
MRP3 | HLA-A24-positive | Phase I UMIN000005678 | 14.0 (9.6–18.5) | 72.7% | [95] | ||
DCs | HCC patients | Phase II | 6 months at 33%, 1 year at 11% | 5.5 | [96] | ||
Ilixadencel | HCC patients | Phase I NCT01974661 | 5.5 | 7.4, for 1 0 × 106 cells 11.8, for 20 × 106 cells | 73% | [97] | |
JX-594 | Advanced HCC | Phase II NCT00554372 | 14.1, for high-dose 6.7, for low-dose | 57%, for high-dose 67%, for low-dose | [98] | ||
JX-594 | Advanced HCC, previously treated with sorafenib | Phase IIb NCT01387555 | 1.8 (1.5–2.8) | 4.2 | [99] | ||
BSC | 2.8 (1.5–NA) | 4.4 (HR, 1.19, p = 0.428) |
Intervention | Cancer Stage | Clinical Phase/Identifier | Progression free survival (PFS) (Months, 95% CI) | Median Overall Survival (OS) (Months, 95% CI) | Response Rates (%, 95% CI) | Bibliography | |
---|---|---|---|---|---|---|---|
CIK, TACE, and RFA | Advance HCC | 17 (10.96–23.04) | 56 (38.09–73.91) | [138] | |||
TACE, RFA | 10 (8.57–11.44) | 31 (24.53–37.47) | |||||
CAR-T cells, cyclophosphamide, and fludarabine | Advanced GPC3+ HCC (Child–Pugh A) | Phase I NCT02905188 NCT03146234 | 3.2 and 3.6 (for two patients) | 9.1 (1.5–20) | Two partial responses | [151] | |
Adjuvant-adoptive immunotherapy | Adjuvant treatment, Resected HCC | 48% (37–59) | [156] | ||||
control | 33% (22–43) |
Intervention | Cancer Stage | Clinical Phase/Identifier | Progression Free Survival (PFS) (Months, 95% CI) | Median Overall Survival (OS) (Months, 95% CI) | Response Rates (%, 95% CI) | Bibliography |
---|---|---|---|---|---|---|
NIVO (1mg/kg), IPI (3mg/kg) | Sorafenib-treated advanced hepatocellular carcinoma patients | NCT01658878 | 54.0 (39.0–68.0) | 23.0 (9.0–NA) | 32% | [157] |
NIVO (3mg/kg), IPI (1mg/kg) | 43.0 (29.0–58.0) | 12.0 (8.0–15.0) | 31% | |||
NIVO (3mg/kg), IPI (1mg/kg) | 49.0 (34.0–64.0) | 13.0 (7.0–33.0) | 31% | |||
NIVO, CABO | Sorafenib or experienced advanced hepatocellular carcinoma patients | NCT01658878 | 5.5 | Not reached | 81% | [158] |
NIVO, IPI, CABO | 6.8 | Not reached | 83% | |||
ATVAC | Resected, invasive HCC | UMIN000005820 | 24.5 (7.8–41.2) | 97.7 (48.6–146.7) | [171] | |
Surgery alone | 12.6 (6.9–18.3) | 41.0 (16.3–65.8) |
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Kole, C.; Charalampakis, N.; Tsakatikas, S.; Vailas, M.; Moris, D.; Gkotsis, E.; Kykalos, S.; Karamouzis, M.V.; Schizas, D. Immunotherapy for Hepatocellular Carcinoma: A 2021 Update. Cancers 2020, 12, 2859. https://doi.org/10.3390/cancers12102859
Kole C, Charalampakis N, Tsakatikas S, Vailas M, Moris D, Gkotsis E, Kykalos S, Karamouzis MV, Schizas D. Immunotherapy for Hepatocellular Carcinoma: A 2021 Update. Cancers. 2020; 12(10):2859. https://doi.org/10.3390/cancers12102859
Chicago/Turabian StyleKole, Christo, Nikolaos Charalampakis, Sergios Tsakatikas, Michail Vailas, Dimitrios Moris, Efthymios Gkotsis, Stylianos Kykalos, Michalis V. Karamouzis, and Dimitrios Schizas. 2020. "Immunotherapy for Hepatocellular Carcinoma: A 2021 Update" Cancers 12, no. 10: 2859. https://doi.org/10.3390/cancers12102859
APA StyleKole, C., Charalampakis, N., Tsakatikas, S., Vailas, M., Moris, D., Gkotsis, E., Kykalos, S., Karamouzis, M. V., & Schizas, D. (2020). Immunotherapy for Hepatocellular Carcinoma: A 2021 Update. Cancers, 12(10), 2859. https://doi.org/10.3390/cancers12102859