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@ARTICLE{Walter:300194,
      author       = {J. D. Walter and M. Beffinger and P. Egloff and I.
                      Zimmermann and L. M. Hürlimann and F. Ackle and M. Seifert
                      and S. Kobold$^*$ and J. Vom Berg and M. A. Seeger},
      title        = {{F}lycodes enable simultaneous preclinical analysis for
                      dozens of antibodies in single cassette-dosed mice.},
      journal      = {Proceedings of the National Academy of Sciences of the
                      United States of America},
      volume       = {122},
      number       = {12},
      issn         = {0027-8424},
      address      = {Washington, DC},
      publisher    = {National Acad. of Sciences},
      reportid     = {DKFZ-2025-00671},
      pages        = {e2426481122},
      year         = {2025},
      abstract     = {Protein therapeutics such as antibodies require in-depth in
                      vivo characterization during development and consequently
                      account for a large proportion of laboratory animal
                      consumption in the pharmaceutical industry. Currently,
                      antibody candidates are exhaustively tested one-by-one in
                      animal models to determine pharmacokinetic and
                      pharmacodynamic (PK/PD) profiles. The simultaneous analysis
                      of antibody mixtures in single animals, called
                      cassette-dosing, could in principle overcome this
                      bottleneck, but is currently limited to small cassette
                      sizes. Here, we demonstrate how the use of genetically
                      encoded peptide tags (flycodes), designed for maximal
                      detectability in liquid chromatography-mass spectrometry,
                      can allow for the simultaneous characterization of large
                      pools of drug candidates, from single cassette-dosed mice.
                      We demonstrate the simultaneous assessment of PK parameters
                      for a group of >20 marketed/development-stage antibodies.
                      Biodistribution experiments in mice bearing EGFR-expressing
                      tumors correctly identified the two pool members recognizing
                      EGFR, while organ analysis registered liver accumulation of
                      an antibody targeting glucagon receptor, a protein
                      profoundly expressed in that organ. In analogy to an
                      early-phase drug development campaign, we performed
                      biophysical and PK analysis for a cassette of 80 unique
                      bispecific DARPin-sybody molecules. The data shown in this
                      study originate from only 18 cassette-dosed mice, thereby
                      demonstrating how flycode technology efficiently advances
                      preclinical discovery pipelines allowing a direct comparison
                      of drug candidates under identical experimental conditions.},
      keywords     = {Animals / Mice / ErbB Receptors: immunology / Humans /
                      Tissue Distribution / Antibodies: immunology /
                      Chromatography, Liquid: methods / Antibodies, Monoclonal:
                      pharmacokinetics / Antibodies, Monoclonal: immunology / Drug
                      Evaluation, Preclinical: methods / Female / antibodies
                      (Other) / cassette dosing (Other) / flycodes (Other) / mass
                      spectrometry (Other) / sybodies (Other) / ErbB Receptors
                      (NLM Chemicals) / Antibodies (NLM Chemicals) / Antibodies,
                      Monoclonal (NLM Chemicals)},
      cin          = {MU01},
      ddc          = {500},
      cid          = {I:(DE-He78)MU01-20160331},
      pnm          = {899 - ohne Topic (POF4-899)},
      pid          = {G:(DE-HGF)POF4-899},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:40096612},
      doi          = {10.1073/pnas.2426481122},
      url          = {https://inrepo02.dkfz.de/record/300194},
}