@article{LuuSchuetzLauthetal.2023,
  author    = {Luu, Maik and Sch{\"u}tz, Burkhard and Lauth, Matthias and Visekruna, Alexander},
  title     = {The impact of gut microbiota-derived metabolites on the tumor immune microenvironment},
  series = {Cancers},
  volume    = {15},
  journal   = {Cancers},
  number    = {5},
  issn      = {2072-6694},
  doi       = {10.3390/cancers15051588},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-311005},
  year      = {2023},
  abstract  = {Prevention of the effectiveness of anti-tumor immune responses is one of the canonical cancer hallmarks. The competition for crucial nutrients within the tumor microenvironment (TME) between cancer cells and immune cells creates a complex interplay characterized by metabolic deprivation. Extensive efforts have recently been made to understand better the dynamic interactions between cancer cells and surrounding immune cells. Paradoxically, both cancer cells and activated T cells are metabolically dependent on glycolysis, even in the presence of oxygen, a metabolic process known as the Warburg effect. The intestinal microbial community delivers various types of small molecules that can potentially augment the functional capabilities of the host immune system. Currently, several studies are trying to explore the complex functional relationship between the metabolites secreted by the human microbiome and anti-tumor immunity. Recently, it has been shown that a diverse array of commensal bacteria synthetizes bioactive molecules that enhance the efficacy of cancer immunotherapy, including immune checkpoint inhibitor (ICI) treatment and adoptive cell therapy with chimeric antigen receptor (CAR) T cells. In this review, we highlight the importance of commensal bacteria, particularly of the gut microbiota-derived metabolites that are capable of shaping metabolic, transcriptional and epigenetic processes within the TME in a therapeutically meaningful way.},
  language  = {en}
}
@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}
}