标题: Targeted delivery of interferon‐α to hepatitis B virus‐infected cells usin [打印本页] 作者: StephenW 时间: 2012-6-11 16:55 标题: Targeted delivery of interferon‐α to hepatitis B virus‐infected cells usin
Targeted delivery of interferon‐α to hepatitis B virus‐infected cells using T cell receptor‐like antibodies
Changhua Ji1,†,*,
Konduru SR Sastry2,
Georg Tiefenthaler3,
Jennifer Cano1,
Tenny Tang1,
ZI Zong Ho2,
Denise Teoh2,
Sandhya Bohini1,
Antony Chen2,
Surya Sankuratri1,
Paul A Macary4,
Patrick Kennedy5,
Han Ma1,
Stefan Ries3,
Klaus Klumpp1,
Erhard Kopetzki3,
Antonio Bertoletti2,6,7,‡,*
DOI: 10.1002/hep.25875
During antiviral therapy, specific delivery of interferon‐α (IFNα) to infected cells may increase its antiviral efficacy, trigger a localized immune reaction and reduce the side effects caused by systemic administration. Two T‐cell receptor‐like antibodies (TCR‐L) able to selectively bind Hepatitis B virus (HBV) infected hepatocytes of chronic hepatitis B patients and recognize core (HBc18‐27) and surface (HBs183‐91) HBV epitopes associated with different Human Leucocytes Antigen (HLA)‐A*2 alleles (A*2:1, A*2:2, A*2:7, A*2:11) were generated. Each antibody was genetically linked to two IFNα molecules to produce TCR‐L/IFNα fusion proteins. We demonstrated that the fusion proteins triggered an IFNα response preferentially on the hepatocytes presenting the correct HBV‐peptide HLA‐complex and that the mechanism of the targeted IFNα response was dependent on the specific binding of the fusion proteins to the HLA/HBV peptide complexes through the TCR‐like variable regions of the antibodies. TCR‐L antibodies can be used to target cytokines to HBV infected hepatocytes in vitro. Fusion of IFNα to TCR‐L decreased the intrinsic biological activity of IFNα but preserved the overall specificity of the protein for the cognate HBV peptide/HLA complexes. This induction of an effective IFNα response selectively in HBV infected cells might have a therapeutic advantage in comparison to the currently used native or pegylated IFNα. (HEPATOLOGY 212.) 作者: StephenW 时间: 2012-6-11 16:56