Transfusion of multi-factors activated immune cells as a novel treatment for patients with chronic hepatitis B

Abstract: Background and objectives: Host–virus interactions play a central role in determining the prognosis of hepatitis B virus infection. Multi-factors activated immune cells (MAICs) are autologous peripheral blood mononuclear cells activated with anti-CD3 monoclonal antibody, interleukin-2 and interferon-γ. The present pilot clinical trial was designed to determine whether adoptively transferred MAICs inhibit the replication of hepatitis B virus and is safe for patients. Study design: Fourteen patients with chronic hepatitis B were enrolled in the study. A total of (1.5–4.0)×109 peripheral blood mononuclear cells were isolated from each patient and activated by anti-CD3 monoclonal antibody, interleukin-2 and interferon-γ in vitro for 10 days to produce MAICs. Cell phenotypes and levels of cytokine secretion were determined during cell culture. Patients were followed up for 1 year after the transfusion of MAICs. Results: After 10 days of culture, peripheral blood mononuclear cells were expanded to a mean fold of 4.68±1.78 and activated effectively, as demonstrated by CD25 expression and cytokine secretion. Cell activation peaked on day 4. All patients accepted the MAICs transfusion with some slight adverse events, and fulminant hepatitis and bilirubinemia were not observed. Significant HBV inhibition was observed in 8 out of 14 patients, in which 5 patients achieved complete response (defined as that serum HBV DNA levels below the detection limit, occurrence of HBeAg seroconversion and normalization of ALT were observed together after MAICs transfusion and kept for at least 6 months) and 3 patients achieved partial response (defined as that serum HBV DNA levels below the detection limit, occurrence of HBeAg disappearance and normalization of ALT were observed together in 6 months after MAICs transfusion, but kept for less than 6 months). Conclusion: These findings strongly suggest that MAICs transfusion, which effectively inhibits the replication of hepatitis B virus, is safe for patients. [Copyright &y& Elsevier]