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@ARTICLE{Hagelstein:302853,
      author       = {I. Hagelstein$^*$ and S. Mattern and K. Wang$^*$ and Y. E.
                      Haueisen$^*$ and S. M. Greiner$^*$ and A. Englisch$^*$ and
                      A. Staebler and S. Singer and M. S. Lutz$^*$},
      title        = {{P}reclinical {E}valuation of a {B}7-{H}3 {T}argeting
                      {A}ntibody {E}nhancing {NK} {C}ell-{M}ediated {C}ytotoxicity
                      for {O}varian {C}ancer {T}reatment.},
      journal      = {ImmunoTargets $\&$ therapy},
      volume       = {14},
      issn         = {2253-1556},
      address      = {Auckland},
      publisher    = {Dove Medical Press Ltd},
      reportid     = {DKFZ-2025-01393},
      pages        = {735 - 753},
      year         = {2025},
      abstract     = {Despite the advancements in treatment, ovarian cancer
                      remains the deadliest gynecological malignancy. The dismal
                      prognosis of the disease necessitates the urgent development
                      of novel therapies. Monoclonal antibodies (mAbs) have
                      transformed cancer treatment, yet their effectiveness in
                      ovarian cancer remains limited. A key mechanism in mAb
                      therapy is antibody-dependent cellular cytotoxicity (ADCC),
                      driven by natural killer (NK) cells targeting tumor cells.
                      Optimization of the Fc domain of mAbs to enhance efficacy
                      has therefore become a subject of extensive research. The
                      costimulatory molecule B7-H3 is overexpressed in various
                      cancers, including ovarian cancer, making it a promising
                      target for anti-tumor mAb immunotherapy. This study
                      evaluates the preclinical potential of an Fc-optimized
                      B7-H3-targeting antibody for ovarian cancer treatment.The
                      expression of B7-H3 was evaluated in tumor samples from 43
                      ovarian cancer patients using immunohistochemistry. A
                      chimeric B7-H3 mAb was developed with a wildtype Fc (8H8-WT)
                      and an Fc-optimized variant (8H8-SDIE) containing
                      S239D/I332E substitutions to enhance CD16 binding and
                      subsequent activation of NK cells. The therapeutic effects
                      of 8H8-SDIE were evaluated through NK cell activation,
                      cytokine release, and cytotoxicity assays.A total of 43
                      ovarian cancer samples were analyzed, and it was found that
                      all of them expressed B7-H3. In addition, 8H8-SDIE was found
                      to demonstrate significantly higher affinity for CD16 than
                      8H8-WT, with minimal effects on other Fc receptors.
                      Functional assays confirmed that 8H8-SDIE enhanced NK cell
                      activation and promoted IFN-γ and TNF release. Furthermore,
                      8H8-SDIE induced robust cytotoxicity against
                      B7-H3-expressing ovarian cancer cells in both short-term and
                      long-term assays.8H8-SDIE has been shown to induce potent NK
                      cell activity, resulting in tumor cell lysis. This finding
                      underscores its promise as an innovative immunotherapeutic
                      approach for the treatment of ovarian cancer.},
      keywords     = {B7-H3 (Other) / NK cell (Other) / immunotherapy (Other) /
                      monoclonal antibody (Other) / ovarian cancer (Other)},
      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:40666622},
      pmc          = {pmc:PMC12262081},
      doi          = {10.2147/ITT.S521008},
      url          = {https://inrepo02.dkfz.de/record/302853},
}