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©The Author(s) 2015.
World J Gastroenterol. Sep 28, 2015; 21(36): 10314-10326
Published online Sep 28, 2015. doi: 10.3748/wjg.v21.i36.10314
Published online Sep 28, 2015. doi: 10.3748/wjg.v21.i36.10314
Author | Country | Year | Indication | Immunotherapy | n | Clinical result | Ref. | |
Cytokine therapy | Llovet et al | Spain | 2000 | Advanced HCC | RCT: IFN-α2b vs no treatment | 30 and 28 | RR: 2/30 (7%), DCR: NANo significant difference in RR or survival | [91] |
Ikeda et al | Japan | 2000 | Adjuvant(resection or ethanol injection) | RCT: IFN-βvs no treatment | 10 and 10 | Significantly longer recurrence-free survival after IFN-β therapy (P = 0.0004 | [92] | |
Sakon et al | Japan | 2002 | Advanced HCC | 5-FU + IFN-α | 11 | RR: 8/11 (73%), DCR: 9/11 (82%)MST: NA | [93] | |
Kubo et a | Japan | 2001 | Adjuvant (resection) | RCT: IFN-α vs. no treatment | 15 and 15 | Significantly longer recurrence-free survival after IFN-α therapy (P = 0.037) | [94] | |
Ladhams et al | Australia | 2002 | Advanced HCC | Dendritic cell pulsed with autologous tumor | 2 | Slowing in the rate of tumor growth in one of two patients | [95] | |
Palmieri et al | Italy | 2002 | Advanced HCC | Low dose IL-2 | 18 | RR: 3/18 (17%), DCR: 16/18 (89%)MST: 24.5 mo | [96] | |
Reinisch et al | Austria | 2002 | Advanced HCC | GM-CSF + IFN-γ | 15 | RR: 1/15 (7%), DCR: 10/15 (67%)MST: 5.5 mo | [97] | |
Feun et al | United States | 2003 | Advanced HCC | Doxorubicin + 5-FU + IFN-α2b | 30 | RR: 2/30 (7%), DCR: 3/30 (10%)MST: 3 mo | [99] | |
Shiratori et al | Japan | 2003 | adjuvant (ethanol injection) | RCT: IFN-αvs no treatment | 49 and 25 | Longer recurrence-free and overall survival after IFN-α therapy (P-value not reported | [100] | |
Patt et al | United States | 2003 | Advanced HCC | 5-FU + IFN-α2b | 43 | RR: 9/36 (25%), DCR 22/36 (61%)MST: 19.5 mo | [49] | |
Komorizono et al | Japan | 2003 | Advanced HCC | Cisplatin + 5-FU + IFN-α | 6 | RR: 2/6 (33%), DCR 3/6 (50%)MST: NA | [50] | |
Sangro et al | Spain | 2004 | Advanced HCC | Intratumoral adenovirus encoding IL-12 genes | 21 (8 HCC) | RR: 1/8 (13%), DCR 7/8 (88%)MST: NA | [102] | |
Yin et al | China | 2005 | Advanced HCC | Cisplatin + doxorubicin + 5-FU + IFN-2α | 26 | RR: 4/26 (15%), DCR 13/26 (50%)MST: 6 mo | [105] | |
Vitale et al | Italy | 2007 | Advanced HCC | 5-FU + IFN-α2b | 9 | RR: 3/9 (33%), DCR 4/9 (44%)MST: 11.5 mo | [108] | |
TAA targeted therapy | Butterfield et al | United States | 2003 | Advanced HCC | AFP peptide vaccination | 6 | RR: 0/6 (0%), DCR 0/6 (0%)MST: 8 mo | [56] |
Kuang et al | China | 2004 | Adjuvant | RCT: autologous formalin-fixed tumor vaccine vs no treatment | 18 and 21 | Significantly longer recurrence-free survival after vaccination (P = 0.003) | [8] | |
Greten et al | Germany | 2010 | Advanced HCC | a telomerase peptide vaccine in combination with a low dose cyclophosphamide | 40 | RR: 0/40 (0%), DCR 17/37 (45.9%)MST: 9.8 mo | [114] | |
Sawada et al | Japan | 2012 | Advanced HCC | GPC3-derived peptide vaccine | 33 | RR: 1/33 (3%), DCR 20/33 (60.6%)MST: 9.0 moOS was significantly longer in patients with high GPC3-specific CTL frequencies | [60] | |
Zhu et al | United States | 2013 | Advanced HCC | GPC3 monoclonal antibody | 20 | RR: 0/20 (0%), DCR 4/20 (60.6%)MST in GPC3 high was likely to be longer than that in GPC3 low or no expression group [49.4 wk vs 13.0 wk] | [61] | |
Immune checkpoint inhibitors | Sangro et al | Spain | 2013 | Advanced HCC | anti-CTLA-4 antibody | 21 | RR: 3/21 (17.6%), DCR 13/21 (76.4%)MST: 8.2 mo | [69] |
Cell transfer immunotherapy | Takayama et al | Japan | 2000 | Adjuvant (resection) | RCT: activated autologous lymphocyte vs no treatment | 76 and 74 | Significantly longer recurrence-free survival after transfer of activated lymphocytes (P = 0.008) | [10] |
Stift et al | Austria | 2003 | Advanced HCC | Dendritic cell pulsed with autologous tumor | 20 (2 HCC) | RR: NA, DCR: NAMST: 10.5 moPersistent AFP over a period of 6 mo in one of two patients | [98] | |
Iwashita et al | Japan | 2003 | Advanced HCC | Dendritic cell pulsed with autologous tumor | 10 (8 HCC) | RR: 0/8 (0%), DCR 6/8 (75%)MST: NA | [101] | |
Shi et al | China | 2004 | Advanced and early HCC | Cytokine induced killer cell | 13 | RR: NA, DCR: NAMST: NA | [78] | |
Mazzolini et al | Spain | 2005 | Advanced HCC | Dendritic cell transfected with adenovirus encoding IL-12 gene | 17 (8 HCC) | RR: 0/0 (0%), DCR: 2/8 (25%)MST: NA | [103] | |
Chi | Taiwan | 2005 | Advanced HCC | Local radiation + intratumoral DC injection | 14 | RR: 2/14 (14%), DCR 9/14 (64%)MST: 5.6 mo | [104] | |
Lee et al | Taiwan | 2005 | Advanced HCC | Dendritic cell pulsed with autologous tumor | 31 | RR: 4/31 (13%), DCR 21/31 (68%)MST: NA | [79] | |
Kumagi et al | Japan | 2005 | Advanced HCC | Intratumoral dendritic cell injection after ethanol injection | 4 | Feasibility study | [106] | |
Butterfield et al | United States | 2006 | Advanced HCC | Dendritic cell pulsed with AFP peptide | 10 | RR: 0/10 (0%), DCR 0/10 (0%)MST: 7.5 mo | [55] | |
Nakamoto et al | Japan | 2007 | Advanced and early HCC | Non-RCT: TACE + dendritic cell vs TACE alone | 10 and 11 | No significant difference in survival | [107] | |
Weng et al | China | 2008 | Adjuvant (TACE and RFA) | RCT: cytokine induced killer cell vs no treatment | 45 and 40 | Significantly longer recurrence-free survival after immunotherapy (P = 0.01) | [109] | |
Hui et al | China | 2009 | Adjuvant (resection) | RCT: cytokine induced killer cell 3 courses vs 6 courses vs no treatment | 41, 43 and 43 | Significantly longer recurrence-free survival after immunotherapy (P = 0.001 and 0.004) | [110] | |
Palmer et al | United Kingdom | 2009 | Advanced HCC | Dendritic cell pulsed with liver tumor cell line lysate (HepG2) | 35 | RR: 1/25 (4%), DCR 7/25 (28%)MST: 5.6 mo | [111] | |
Olioso et al | Italy | 2009 | Advanced HCC | Cytokine induced killer cell + IFN-α | 12 (1 HCC) | Complete responseSurvival time: 33 mo (alive) | [112] | |
Hao et al | China | 2010 | Advanced HCC | Non-RCT: TACE + cytokine induced killer cell vs TACE alone | 72 and 74 | Significantly longer survival after combination therapy (P < 0.001) | [113] | |
Ma et al | China | 2010 | Adjuvant (RFA) | RFA and autologous RetroNectin activated killer cells | 7 | During a 7-mo follow-up, no severe adverse events, recurrences, or deaths | [115] | |
Nakamoto et al | Japan | 2011 | Adjuvant (TACE) | TACE + OK432-stimulated DCs vs TACE alone | 13 and 22 | Significantly longer recurrence-free survival after immunotherapy (P = 0.046) | [80] | |
Zhou et al | China | 2011 | HCC with hepatitis B (PMWA) | Immature DCs, CIK, CTL and tumor lysate-pulsed DC | 10 | This Phase I study revealed this therapy was safe and increased the percentage of effector cells | [116] | |
Qiu et al | China | 2011 | Adjuvant (resection) | RCT: TAA-pulsed DC and CIK vs no treatment | 9 vs 9 | Significantly longer recurrence-free survival after immunotherapy (P = 0.00121) | [117] | |
Tada et al | Japan | 2012 | Advanced HCC | TACE + multiple TAA-pulsed DC | 5 | This Phase I/II study revealed this therapy was safe and increased the percentage of effector cells | [118] | |
Cui et al | China | 2014 | Adjuvant (RFA) | RFA + NK cells, γδT cells and CIK cells vs RFA alone | 30 and 32 | Significantly longer recurrence-free survival after immunotherapy | [76] |
- Citation: Tsuchiya N, Sawada Y, Endo I, Uemura Y, Nakatsura T. Potentiality of immunotherapy against hepatocellular carcinoma. World J Gastroenterol 2015; 21(36): 10314-10326
- URL: https://www.wjgnet.com/1007-9327/full/v21/i36/10314.htm
- DOI: https://dx.doi.org/10.3748/wjg.v21.i36.10314