PMID- 22684948
OWN - NLM
STAT- MEDLINE
DCOM- 20130228
LR  - 20130520
IS  - 1527-3350 (Electronic)
IS  - 0270-9139 (Linking)
VI  - 56
IP  - 6
DP  - 2012 Dec
TI  - Targeted delivery of interferon-alpha to hepatitis B virus-infected cells using 
      T-cell receptor-like antibodies.
PG  - 2027-38
LID - 10.1002/hep.25875 [doi]
AB  - During antiviral therapy, specific delivery of interferon-alpha (IFNalpha) 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 
      leukocyte antigen (HLA)-A*02 alleles (A*02:01, A*02:02, A*02:07, A*02:11) were 
      generated. Each antibody was genetically linked to two IFNalpha molecules to produce 
      TCR-L/IFNalpha fusion proteins. We demonstrate that the fusion proteins triggered an 
      IFNalpha response preferentially on the hepatocytes presenting the correct 
      HBV-peptide HLA-complex and that the mechanism of the targeted IFNalpha 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. CONCLUSION: 
      TCR-L antibodies can be used to target cytokines to HBV-infected hepatocytes in 
      vitro. Fusion of IFNalpha to TCR-L decreased the intrinsic biological activity of 
      IFNalpha but preserved the overall specificity of the protein for the cognate HBV 
      peptide/HLA complexes. This induction of an effective IFNalpha response selectively 
      in HBV-infected cells might have a therapeutic advantage in comparison to the 
      currently used native or pegylated IFNalpha.
CI  - Copyright (c) 2012 American Association for the Study of Liver Diseases.
FAU - Ji, Changhua
AU  - Ji C
AD  - Virology Discovery, Roche Pharma Research and Early Development, Nutley, NJ, USA. 
      changhua.ji@roche.com
FAU - Sastry, Konduru S R
AU  - Sastry KS
FAU - Tiefenthaler, Georg
AU  - Tiefenthaler G
FAU - Cano, Jennifer
AU  - Cano J
FAU - Tang, Tenny
AU  - Tang T
FAU - Ho, Zi Zong
AU  - Ho ZZ
FAU - Teoh, Denise
AU  - Teoh D
FAU - Bohini, Sandhya
AU  - Bohini S
FAU - Chen, Antony
AU  - Chen A
FAU - Sankuratri, Surya
AU  - Sankuratri S
FAU - Macary, Paul A
AU  - Macary PA
FAU - Kennedy, Patrick
AU  - Kennedy P
FAU - Ma, Han
AU  - Ma H
FAU - Ries, Stefan
AU  - Ries S
FAU - Klumpp, Klaus
AU  - Klumpp K
FAU - Kopetzki, Erhard
AU  - Kopetzki E
FAU - Bertoletti, Antonio
AU  - Bertoletti A
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20120712
PL  - United States
TA  - Hepatology
JT  - Hepatology (Baltimore, Md.)
JID - 8302946
RN  - 0 (Antibodies, Viral)
RN  - 0 (Antiviral Agents)
RN  - 0 (Chemokines)
RN  - 0 (Drug Carriers)
RN  - 0 (HLA-A Antigens)
RN  - 0 (Interferon-alpha)
RN  - 0 (Recombinant Fusion Proteins)
SB  - IM
MH  - Animals
MH  - Antibodies, Viral/immunology/*pharmacology
MH  - Antiviral Agents/*pharmacology
MH  - Artificial Gene Fusion
MH  - CD8-Positive T-Lymphocytes/drug effects
MH  - Chemokines/metabolism
MH  - Drug Carriers/pharmacology
MH  - HLA-A Antigens/*immunology
MH  - Hep G2 Cells
MH  - Hepatitis B/drug therapy/*immunology/virology
MH  - Hepatitis B virus/genetics/*immunology
MH  - Humans
MH  - Interferon-alpha/*pharmacology
MH  - Lymphocyte Activation/drug effects
MH  - Mice
MH  - Recombinant Fusion Proteins/*pharmacology
EDAT- 2012/06/12 06:00
MHDA- 2013/03/01 06:00
CRDT- 2012/06/12 06:00
PHST- 2012/02/22 00:00 [received]
PHST- 2012/05/21 00:00 [accepted]
PHST- 2012/06/12 06:00 [entrez]
PHST- 2012/06/12 06:00 [pubmed]
PHST- 2013/03/01 06:00 [medline]
AID - 10.1002/hep.25875 [doi]
PST - ppublish
SO  - Hepatology. 2012 Dec;56(6):2027-38. doi: 10.1002/hep.25875. Epub 2012 Jul 12.