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@ARTICLE{Pahl:132942,
      author       = {J. Pahl$^*$ and J. Koch and J. Götz$^*$ and A. Arnold$^*$
                      and U. Reusch and T. Gantke and E. Rajkovic and M. Treder
                      and A. Cerwenka$^*$},
      title        = {{CD}16{A} {A}ctivation of {NK} {C}ells {P}romotes {NK}
                      {C}ell {P}roliferation and {M}emory-{L}ike {C}ytotoxicity
                      against {C}ancer {C}ells.},
      journal      = {Cancer immunology research},
      volume       = {6},
      number       = {5},
      issn         = {2326-6074},
      address      = {Philadelphia, Pa.},
      publisher    = {AACR},
      reportid     = {DKFZ-2018-00581},
      pages        = {517 - 527},
      year         = {2018},
      abstract     = {CD16A is a potent cytotoxicity receptor on human natural
                      killer (NK) cells, which can be exploited by therapeutic
                      bispecific antibodies. So far, the effects of CD16A-mediated
                      activation on NK cell effector functions beyond classical
                      antibody-dependent cytotoxicity have remained poorly
                      elucidated. Here, we investigated NK cell responses after
                      exposure to therapeutic antibodies such as the tetravalent
                      bispecific antibody AFM13 (CD30/CD16A), designed for the
                      treatment of Hodgkin lymphoma and other CD30+ lymphomas. Our
                      results reveal that CD16A engagement enhanced subsequent
                      IL2- and IL15-driven NK cell proliferation and expansion.
                      This effect involved the upregulation of CD25 (IL2Rα) and
                      CD132 (γc) on NK cells, resulting in increased sensitivity
                      to low-dose IL2 or to IL15. CD16A engagement initially
                      induced NK cell cytotoxicity. The lower NK cell reactivity
                      observed 1 day after CD16A engagement could be recovered by
                      reculture in IL2 or IL15. After reculture in IL2 or IL15,
                      these CD16A-experienced NK cells exerted more vigorous IFNγ
                      production upon restimulation with tumor cells or cytokines.
                      Importantly, after reculture, CD16A-experienced NK cells
                      also exerted increased cytotoxicity toward different tumor
                      targets, mainly through the activating NK cell receptor
                      NKG2D. Our findings uncover a role for CD16A engagement in
                      priming NK cell responses to restimulation by cytokines and
                      tumor cells, indicative of a memory-like functionality. Our
                      study suggests that combination of AFM13 with IL2 or IL15
                      may boost NK cell antitumor activity in patients by
                      expanding tumor-reactive NK cells and enhancing NK cell
                      reactivity, even upon repeated tumor encounters. Cancer
                      Immunol Res; 6(5); 517-27. ©2018 AACR.},
      cin          = {D080},
      ddc          = {610},
      cid          = {I:(DE-He78)D080-20160331},
      pnm          = {314 - Tumor immunology (POF3-314)},
      pid          = {G:(DE-HGF)POF3-314},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:29514797},
      doi          = {10.1158/2326-6066.CIR-17-0550},
      url          = {https://inrepo02.dkfz.de/record/132942},
}