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@ARTICLE{Quitt:170228,
author = {O. Quitt and S. Luo and M. Meyer$^*$ and Z. Xie and F.
Golsaz-Shirazi and E. Loffredo-Verde and J. Festag and J. H.
Bockmann and L. Zhao and D. Stadler and W.-M. Chou and R.
Tedjokusumo and J. M. Wettengel and C. Ko and E. Noeßner
and N. Bulbuc$^*$ and F. Shokri and S. Lüttgau and M.
Heikenwälder and F. Bohne and G. Moldenhauer$^*$ and F.
Momburg$^*$ and U. Protzer},
title = {{T} cell engager antibodies enable {T} cells to control
{HBV} infection and to target {HB}s{A}g-positive hepatoma in
mice.},
journal = {Journal of hepatology},
volume = {75},
number = {5},
issn = {0168-8278},
address = {[S.l.]},
publisher = {Wiley-Blackwell},
reportid = {DKFZ-2021-01836},
pages = {1058-1071},
year = {2021},
note = {2021 Nov;75(5):1058-1071},
abstract = {Current antiviral therapies control but rarely eliminate
HBV, leaving chronic HBV carriers at risk of developing
hepatocellular carcinoma (HCC). Lacking or dysfunctional
virus-specific adaptive immunity prevents control of HBV and
allows the virus to persist. Restoring antiviral T cell
immunity could lead to HBV elimination and cure of
chronically infected patients.We constructed bispecific T
cell engager antibodies that are designed to induce
antiviral immunity through simultaneous binding of HBV
envelope proteins (HBVenv) on infected hepatocytes and CD3
or CD28 on T cells. T cell engager antibodies were employed
in co-cultures with healthy donor lymphocytes and
HBV-infected target cells. Activation of the T cell response
was determined by detection of pro-inflammatory cytokines,
effector function (by cytotoxicity) and antiviral effects.
To study in vivo efficacy, immune-deficient mice were
transplanted with HBVenv-positive and -negative hepatoma
cells.The 2 T cell engager antibodies synergistically
activated T cells to become polyfunctional effectors that in
turn elicited potent antiviral effects by killing infected
cells and in addition controlled HBV via non-cytolytic,
cytokine-mediated antiviral mechanisms. In vivo in mice,
the antibodies attracted T cells specifically to the tumors
expressing HBVenv resulting in T cell activation, tumor
infiltration and reduction of tumor burden.This study
demonstrates that the administration of HBVenv-targeting T
cell engager antibodies facilitates a robust T cell
redirection towards HBV-positive target cells and provides a
feasible and promising approach for the treatment of chronic
viral hepatitis and HBV-associated HCC.T cell engager
antibodies are an interesting, novel therapeutic tool to
restore immunity in patients with chronic hepatitis B. As
bispecific antibodies, they bind envelope proteins on the
surface of the hepatitis B virus (HBV) and CD3 or CD28 on T
cells. This way, they induce a potent antiviral and
cytotoxic T cell response that leads to the elimination of
HBV-positive cells. These bispecific T cell engager
antibodies are exciting therapeutic candidates for chronic
hepatitis B and HBV-associated hepatocellular carcinoma.},
keywords = {T cell redirection (Other) / Viral hepatitis (Other) /
bispecific T cell engager (Other) / immunotherapy (Other)},
cin = {D050 / D121},
ddc = {610},
cid = {I:(DE-He78)D050-20160331 / I:(DE-He78)D121-20160331},
pnm = {314 - Immunologie und Krebs (POF4-314)},
pid = {G:(DE-HGF)POF4-314},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:34171437},
doi = {10.1016/j.jhep.2021.06.022},
url = {https://inrepo02.dkfz.de/record/170228},
}