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


METHODS
Fourteen patients with chronic hepatitis B were enrolled in the study. A total of (1.5-4.0)x10(9) peripheral blood mononuclear cells were isolated from each patient and activated by anti-CD3 monoclonal antibody, interleukin-2 and interferon-gamma 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).


CONCLUSIONS
These findings strongly suggest that MAICs transfusion, which effectively inhibits the replication of hepatitis B virus, is safe for patients.
Sun
Jing
J
Hepatology Institute, Peking University Health Science Center People's Hospital, Beijing 100044, China.
Gao
Yan
Y
Chen
Hong-Song
HS
Wang
Song-Xia
SX
Li
Ruo-Bing
RB
Jiang
Dong
D
Wei
Lai
L
Wang
Yu
Y
D000293:Adolescent; D000328:Adult; D000911:Antibodies, Monoclonal / Q000276:immunology; D017252:CD3 Complex / Q000276:immunology; D002478:Cells, Cultured; D005260:Female; D006515:Hepatitis B virus / Q000276:immunology / Q000502:physiology; D019694:Hepatitis B, Chronic / Q000276:immunology / Q000628:therapy* / Q000821:virology; D006801:Humans; D007371:Interferon-gamma / Q000276:immunology; D007376:Interleukin-2 / Q000276:immunology; D007937:Leukapheresis; D017708:Leukocyte Transfusion / Q000009:adverse effects; D007963:Leukocytes, Mononuclear / Q000276:immunology*; D008213:Lymphocyte Activation / Q000276:immunology*; D008297:Male; D010865:Pilot Projects; D016896:Treatment Outcome
D000911:Antibodies, Monoclonal; D017252:CD3 Complex; D007376:Interleukin-2; D007371:Interferon-gamma