Effect of treatment of autologous cytokine-induced killer cells(CIKs) on the suppression of hepatitis B virus and its mechanism

Objective To investigate the effect of cytokine-induced killer cells(CIKs) treatment on the suppression of HBV replication and its mechanism.Methods Sixteen patients with chronic hepatitis B(CHB),hospitalized from Apr.2009 to Dec.2010 in 302 Hospital,having not received antiviral drugs treatment or immunotherapy,were enrolled in present study.The peripheral blood mononuclear cells(PBMC) were collected and induced into CIKs by cytokine cocktail,and transfused back to patients via intravenous injection.The effects of CIK-cell transfusion on HBV DNA load,changes of the cell frequency of CD3+CD56+,myeloid dendritic cells(mDCs) and plasmacytoid dendritic cells(pDCs) were observed during a 24-week follow-up period.Results After autologous CIKs transfusion,the level of HBV DNA decreased in 9 sustained virological responders at 4th,12th and 24th week(5.70,5.09 and 4.08log10 copies/ml,respectively,P < 0.05 or P < 0.01).The HBV DNA level showed no difference compared with the baseline(6.39log10 copies/ml) in other 7 non-virological responders.After 14d of inducible cultivation,the frequency of CIK-CD3+CD56+ cells,which were the main effectors,was significantly higher in virological responders(17.2%) than in non-virological responders(9.0%,P < 0.05).After CIKs transfusion,the frequency of pDC in virological responders increased from 0.27% at the baseline to 0.39% at 4-week and 0.34% at 8-week(P < 0.05),but no differences were found in non-virological responders during the follow up period.No serious clinical adverse effects were observed.Conclusions CIKs treatment can effectively inhibit the HBV replication,and it is safe for CHB patients.The mechanism of CIKs treatment on the suppression of HBV is partially attributable to the increased frequency of pDCs.