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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},
}