Safety and immunogenicity of hepatitis B surface antigen-pulsed dendritic cells in patients with chronic hepatitis B.
The immune modulator capacity of antigen-pulsed dendritic cells (DC) has been documented in patients with cancers and in animal models of chronic viral infections. Cancer antigen-pulsed DC are now used for treating patients with cancer. But viral antigen-pulsed DC are not used in chronic viral-infected patients because safety of antigen-pulsed DC has not been evaluated in these patients. DC were isolated from human peripheral blood mononuclear cells by culturing with human-grade granulocyte-macrophage colony stimulating factor and interleukin-4. Human blood DC were cultured with hepatitis B surface antigen (HBsAg) for 8h to prepare HBsAg-pulsed DC. After immunogenicity assessment of HBsAg-pulsed DC in vitro, five million HBsAg-pulsed DC were administered intradermally to five patients with chronic hepatitis B (CHB) 1-3 times. HBsAg-pulsed DC were immunogenic in nature because they produced significantly higher levels of interleukin-12 and interferon-γ compared to unpulsed DC (P<0.05). Also, HBsAg-pulsed DC induced proliferation of HBsAg-specific T lymphocytes in vitro. CHB patients injected with HBsAg-pulsed DC did not exhibit generalized inflammation, exacerbation of liver damage, abnormal kidney function, or features of autoimmunity. Administration of HBsAg-pulsed DC induced anti-HBs in two patients and HBsAg-specific cellular immunity in 1 patient. This is the first study about preparation of antigen-pulsed DC using human consumable materials for treating patients with CHB. Because HBsAg-pulsed DC were safe for all patients with CHB and had immune modulation capacity in some patients, phase I and phase II clinical trials with antigen-pulsed DC in CHB and other chronic infections are warranted.
Akbar
S M F
SM
Department of Medical Sciences, Toshiba General Hospital, Tokyo, Japan.
Furukawa
S
S
Horiike
N
N
Abe
M
M
Hiasa
Y
Y
Onji
M
M
D000328:Adult; D000410:Alanine Transaminase / Q000097:blood; D001806:Blood Urea Nitrogen; D004279:DNA, Viral / Q000032:analysis; D003713:Dendritic Cells / Q000276:immunology*; D005260:Female; D006514:Hepatitis B Surface Antigens / Q000008:administration & dosage / Q000276:immunology*; D017325:Hepatitis B Vaccines / Q000008:administration & dosage*; D006515:Hepatitis B virus / Q000276:immunology; D019694:Hepatitis B, Chronic / Q000517:prevention & control* / Q000628:therapy; D006801:Humans; D007111:Immunity, Cellular; D007167:Immunotherapy; D007371:Interferon-gamma / Q000276:immunology; D018664:Interleukin-12 / Q000276:immunology; D008297:Male; D008875:Middle Aged; D010865:Pilot Projects
D004279:DNA, Viral; D006514:Hepatitis B Surface Antigens; D017325:Hepatitis B Vaccines; D018664:Interleukin-12; D007371:Interferon-gamma; D000410:Alanine Transaminase