Safety and immunogenicity of hepatitis B surface antigen-pulsed dendritic cells in patients with chronic hepatitis B

[Guest guest]

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.

[Guest guest]

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.