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<http://onlinelibrary.wiley.com/doi/10.1111/j.1365-2893.2010.01320.x/abstract>
Safety and immunogenicity of hepatitis B surface antigen-pulsed dendritic
cells in patients with chronic hepatitis B
S. M. F. Akbar1,2, S. Furukawa1, N. Horiike1, M. Abe1, Y. Hiasa1, M.
Onji1Article first published online: 17 MAY 2010
DOI: 10.1111/j.1365-2893.2010.01320.x
© 2010 Blackwell Publishing Ltd
Issue
Journal of Viral Hepatitis
Volume 18, Issue 6, pages 408–414, June 2011
Summary. 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 8 h 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.
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