抄録 |
Treatments targeting hepatocellular carcinoma (HCC) in advanced stage are often discontinued due to systemic adverse effect. Immunotherapy is a promising treatment which specifically targets HCC. A survey on ClinicalTrials.gov or UMIN database searching for cell-based immunotherapy and HCC indicates that 8 and 7 trials, respectively, including dendritic cell (DC), αβT-cell, NK-cell, NKT-cell and γδT-cell therapy have been registered. Of those, DC-based therapy is the only treatment which has already shown a clinical benefit in prostate cancer patients and been approved by Food and Drug Administration in USA. We found in mouse hepatoma model that intravenous injection of ECI301, an active variant of human CC chemokine ligand 3 which increases circulating DC, or adoptive transfer of DC stimulated with OK-432, penicillin-treated streptococcus pyogenes, promotes T-cell mediated anti-tumor immunity and tumor regression after radio-frequency ablation (RFA). Based on these results in pre-clinical mouse studies, we adoptively transferred OK-432-stimulated DC in 13 HCC patients after transcatheter arterial embolization (TAE). The administration of OK432-stimulated DCs was feasible and safe. In addition, Kaplan-Meier analysis revealed prolonged recurrence-free survival of patients treated with OK432-treated DC plus TAE compared with 11 historical controls treated with TAE only (1-year recurrence-free survival 84.6% vs 18.2%, P = 0.0050, log-rank test). Adoptive transfer of OK-432-stimulated DC after RFA in 14 HCC patients was also conducted safely. Thus, DC-based immunotherapy might exert beneficial anti-tumor effect on HCC patients. |