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@ARTICLE{Zekri:271007,
      author       = {L. Zekri$^*$ and M. S. Lutz$^*$ and N. Prakash$^*$ and T.
                      Manz$^*$ and B. Klimovich$^*$ and S. Mueller$^*$ and S.
                      Hoerner$^*$ and I. Hagelstein$^*$ and M. Engel$^*$ and A.
                      Chashchina$^*$ and M. Pfluegler$^*$ and J. Heitmann$^*$ and
                      G. Jung$^*$ and H. Salih$^*$},
      title        = {{A}n optimized {I}g{G}-based {B}7-{H}3x{CD}3 bispecific
                      antibody for treatment of gastrointestinal cancers.},
      journal      = {Molecular therapy},
      volume       = {31},
      number       = {4},
      issn         = {1525-0016},
      address      = {New York, NY},
      publisher    = {Nature Publ. Group},
      reportid     = {DKFZ-2023-00360},
      pages        = {1033-1045},
      year         = {2023},
      note         = {2023 Apr 5;31(4):1033-1045},
      abstract     = {T cell-based immunotherapy has revolutionized oncological
                      treatment. However, many patients do not respond to
                      treatment, and long-term remissions remain rare,
                      particularly in gastrointestinal cancers like colorectal
                      cancer (CRC). B7-H3 is overexpressed in multiple cancer
                      entities including CRC on both, tumor cells and tumor
                      vasculature, the latter facilitating influx of effector
                      cells into the tumor site upon therapeutic targeting. We
                      generated a panel of T cell-recruiting B7-H3xCD3 bispecific
                      antibodies (bsAbs) and show that targeting a
                      membrane-proximal B7-H3 epitope allows for a 100-fold
                      reduction of CD3 affinity. In vitro, our lead compound CC-3
                      showed superior tumor cell killing, T cell activation,
                      proliferation and memory formation, whereas undesired
                      cytokine release was reduced. In vivo, CC-3 mediated potent
                      antitumor activity in three independent models using
                      immunocompromised mice adoptively transferred with human
                      effector cells with regard to prevention of lung metastasis
                      and flank tumor growth as well as elimination of large
                      established tumors. Thus, fine-tuning of both, target and
                      CD3 affinities as well as binding epitopes allowed for the
                      generation of a B7-H3xCD3 bsAb with promising therapeutic
                      activity. CC-3 is presently undergoing GMP production to
                      enable evaluation in a clinical 'first in human' study in
                      CRC.},
      cin          = {TU01},
      ddc          = {610},
      cid          = {I:(DE-He78)TU01-20160331},
      pnm          = {899 - ohne Topic (POF4-899)},
      pid          = {G:(DE-HGF)POF4-899},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:36793213},
      doi          = {10.1016/j.ymthe.2023.02.010},
      url          = {https://inrepo02.dkfz.de/record/271007},
}