@article{RydzekNerreterPengetal.2019,
  author    = {Rydzek, Julian and Nerreter, Thomas and Peng, Haiyong and Jutz, Sabrina and Leitner, Judith and Steinberger, Peter and Einsele, Hermann and Rader, Christoph and Hudecek, Michael},
  title     = {Chimeric Antigen Receptor Library Screening Using a Novel NF-kappa B/NFAT Reporter Cell Platform},
  series = {Molecular Therapy},
  volume    = {27},
  journal   = {Molecular Therapy},
  number    = {2},
  doi       = {10.1016/j.ymthe.2018.11.015},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-227193},
  pages     = {287-299},
  year      = {2019},
  abstract  = {Chimeric antigen receptor (CAR)-T cell immunotherapy is under intense preclinical and clinical investigation, and it involves a rapidly increasing portfolio of novel target antigens and CAR designs. We established a platform that enables rapid and high-throughput CAR-screening campaigns with reporter cells derived from the T cell lymphoma line Jurkat. Reporter cells were equipped with nuclear factor kappa B (NF kappa B) and nuclear factor of activated T cells (NFAT) reporter genes that generate a duplex output of enhanced CFP (ECFP) and EGFP, respectively. As a proof of concept, we modified reporter cells with CD19-specific and ROR1-specific CARs, and we detected high-level reporter signals that allowed distinguishing functional from non-functional CAR constructs. The reporter data were highly reproducible, and the time required for completing each testing campaign was substantially shorter with reporter cells (6 days) compared to primary CAR-T cells (21 days). We challenged the reporter platform to a large-scale screening campaign on a ROR1-CAR library, and we showed that reporter cells retrieved a functional CAR variant that was present with a frequency of only 6 in 1.05 x 10(6). The data illustrate the potential to implement this reporter platform into the preclinical development path of novel CAR-T cell products and to inform and accelerate the selection of lead CAR candidates for clinical translation.},
  language  = {en}
}