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@ARTICLE{Thomas:301478,
      author       = {M. Thomas and R. Brabenec and L. Gregor and D. Andreu-Sanz
                      and E. Carlini and P. J. Müller and A. Gottschlich and D.
                      Simnica and S. Kobold$^*$ and C. Marr},
      title        = {{T}he role of single cell transcriptomics for efficacy and
                      toxicity profiling of chimeric antigen receptor ({CAR}) {T}
                      cell therapies.},
      journal      = {Computers in biology and medicine},
      volume       = {192},
      number       = {Pt B},
      issn         = {0010-4825},
      address      = {Amsterdam [u.a.]},
      publisher    = {Elsevier Science},
      reportid     = {DKFZ-2025-01020},
      pages        = {110332},
      year         = {2025},
      abstract     = {CAR T cells are genetically modified T cells that target
                      specific epitopes. CAR T cell therapy has proven effective
                      in difficult-to-treat B cell cancers and is now expanding
                      into hematology and solid tumors. To date, approved CAR
                      therapies target only two specific epitopes on cancer cells.
                      Identifying more suitable targets is challenged by the lack
                      of truly cancer-specific structures and the potential for
                      on-target off-tumor toxicity. We analyzed gene expression of
                      potential targets in single-cell data from cancer and
                      healthy tissues. Because safety and efficacy can ultimately
                      only be defined clinically, we selected approved and
                      investigational targets for which clinical trail data are
                      available. We generated atlases using >300,000 cells from 48
                      patients with follicular lymphoma, multiple myeloma, and
                      B-cell acute lymphoblastic leukemia, and integrated over 3
                      million cells from 35 healthy tissues, harmonizing datasets
                      from over 300 donors. To contextualize findings, we compared
                      target expression patterns with outcome data from clinical
                      trials, linking target profiles to efficacy and toxicity,
                      and ranked 15 investigational targets based on their
                      similarity to approved ones. Target expression did not
                      significantly correlate with reported clinical toxicities in
                      patients undergoing therapy. This may be attributed to the
                      intricate interplay of patient-specific variables, the
                      limited amount of metadata, and the complexity underlying
                      toxicity. Nevertheless, our study serves as a resource for
                      retrospective and prospective target evaluation to improve
                      the safety and efficacy of CAR therapies.},
      keywords     = {Adoptive T cell therapy (Other) / CAR T cell therapy
                      (Other) / Chimeric antigen receptor (Other) / Off-tumor
                      toxicity (Other) / Single-cell sequencing (Other) / Target
                      antigen (Other)},
      cin          = {MU01},
      ddc          = {570},
      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:40375426},
      doi          = {10.1016/j.compbiomed.2025.110332},
      url          = {https://inrepo02.dkfz.de/record/301478},
}