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@ARTICLE{Triller:241137,
      author       = {G. Triller$^*$ and E. P. Vlachou$^*$ and H. Hashemi and M.
                      van Straaten$^*$ and J. P. Zeelen$^*$ and Y. Kelemen and C.
                      Baehr and C. L. Marker and S. Ruf$^*$ and A. Svirina$^*$ and
                      M. Chandra$^*$ and K. Urban$^*$ and A. Gkeka$^*$ and S.
                      Kruse and A. Baumann$^*$ and A. K. Miller$^*$ and M. Bartel
                      and M. Pravetoni and C. E. Stebbins$^*$ and F. N.
                      Papavasiliou$^*$ and J. P. Verdi$^*$},
      title        = {{A} trypanosome-derived immunotherapeutics platform elicits
                      potent high-affinity antibodies, negating the effects of the
                      synthetic opioid fentanyl.},
      journal      = {Cell reports},
      volume       = {42},
      number       = {2},
      issn         = {2211-1247},
      address      = {[New York, NY]},
      publisher    = {Elsevier},
      reportid     = {DKFZ-2023-00250},
      pages        = {112049},
      year         = {2023},
      note         = {#EA:D150#LA:D150#},
      abstract     = {Poorly immunogenic small molecules pose challenges for the
                      production of clinically efficacious vaccines and
                      antibodies. To address this, we generate an immunization
                      platform derived from the immunogenic surface coat of the
                      African trypanosome. Through sortase-based conjugation of
                      the target molecules to the variant surface glycoprotein
                      (VSG) of the trypanosome surface coat, we develop
                      VSG-immunogen array by sortase tagging (VAST). VAST elicits
                      antigen-specific memory B cells and antibodies in a murine
                      model after deploying the poorly immunogenic molecule
                      fentanyl as a proof of concept. We also develop a
                      single-cell RNA sequencing (RNA-seq)-based computational
                      method that synergizes with VAST to specifically identify
                      memory B cell-encoded antibodies. All computationally
                      selected antibodies bind to fentanyl with picomolar
                      affinity. Moreover, these antibodies protect mice from
                      fentanyl effects after passive immunization, demonstrating
                      the ability of these two coupled technologies to elicit
                      therapeutic antibodies to challenging immunogens.},
      keywords     = {CP: Immunology (Other) / Trypanosoma brucei (Other) /
                      antibody repertoire analysis (Other) / fentanyl (Other) /
                      humoral immunity (Other) / immunological memory (Other) /
                      opioid overdose (Other) / sortase (Other) / variant surface
                      glycoprotein (Other)},
      cin          = {D150 / D160 / A390},
      ddc          = {610},
      cid          = {I:(DE-He78)D150-20160331 / I:(DE-He78)D160-20160331 /
                      I:(DE-He78)A390-20160331},
      pnm          = {314 - Immunologie und Krebs (POF4-314)},
      pid          = {G:(DE-HGF)POF4-314},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:36719797},
      doi          = {10.1016/j.celrep.2023.112049},
      url          = {https://inrepo02.dkfz.de/record/241137},
}