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@ARTICLE{Moser:298948,
      author       = {L. M. Moser$^*$ and C. Heim and S. E. Koschade$^*$ and P.
                      Wendel$^*$ and S. Bozkurt and S. Harenkamp and H. Kreyenberg
                      and M. Merker and C. Münch and E. Gradhand and M.
                      Vogler$^*$ and E. Ullrich$^*$ and H. Bönig and J.-H.
                      Klusmann$^*$ and P. Bader$^*$ and W. S. Wels$^*$ and E.
                      Rettinger$^*$},
      title        = {{CAR}-{CIK} vs. {CAR}-{T}: benchmarking novel
                      cytokine-induced killer cells as solid tumor immunotherapy
                      in {E}rb{B}2+ rhabdomyosarcoma.},
      journal      = {Frontiers in immunology},
      volume       = {16},
      issn         = {1664-3224},
      address      = {Lausanne},
      publisher    = {Frontiers Media},
      reportid     = {DKFZ-2025-00382},
      pages        = {1485817},
      year         = {2025},
      abstract     = {CAR-T cell therapy, though successful in hematologic
                      malignancies, faces challenges in solid tumors due to
                      limitations of autologous T cells. Cytokine-induced killer
                      (CIK) cells can be given safely across allogeneic barriers
                      and constitute alternative effector cells generated from
                      healthy donors. CIK cells are a heterogenous population of
                      predominantly T cells with a mixed natural killer (NK)
                      phenotype and combine non-MHC-restricted cytotoxicity with
                      potent anti-tumor capacity of the adaptive immune system.
                      Here, we characterize and compare efficacy, phenotypic
                      subpopulations and modes of action of CAR-CIK cells and
                      conventional CAR-T cells from same-donor samples in ErbB2+
                      rhabdomyosarcoma (RMS).To benchmark CAR-CIK against
                      conventional CAR-T cells, effector cells were generated from
                      same-donor samples and lentivirally transduced with a second
                      generation CD28-CD3ζ CAR. Effector subpopulations and their
                      dynamics upon target cell exposure were phenotypically
                      characterized by flow cytometry. Efficacy was assessed in
                      human ErbB2+ RMS cancer cell lines and primary patient
                      samples in vitro and ex vivo using cytotoxicity and spheroid
                      co-incubation assays. Modes of action were assessed by
                      comparing cytokine secretion profiles using bead-based
                      multiplexed flow cytometry and by liquid chromatography mass
                      spectrometry whole cell proteomics. Finally, we used an in
                      vivo model of RMS mimicking minimal metastatic residual
                      disease to compare anti-tumor potency of CAR-CIK vs. CAR-T
                      cells and to assess their target organ infiltration.In vitro
                      assays demonstrated superior cytotoxicity of CAR-CIK cells
                      against RMS cell lines and primary tumor samples. Long-term
                      co-incubation with tumor spheroids led to expansion of
                      CAR-CIK cells and enrichment of CD3+CD56+ TNK cells. CAR-CIK
                      cell cytokine signature showed significantly increased
                      secretion of effector molecules like interferon-γ, perforin
                      and granulysin, and lower secretion of Th2 cytokines IL-2,
                      IL-4 and IL-10. Whole cell proteomics showed corresponding
                      upregulation of chemokine signaling and NK-cytotoxicity
                      pathways in CAR-CIK cells. In NSG mice xenografted with
                      ErbB2+ RMS, a single injection of either CAR-effector cells
                      strongly impeded metastatic tumor development and
                      significantly improved survival.Our results demonstrate that
                      CAR-CIK cells are at least equipotent to CAR-T cells.
                      Combined with their favorable safety profile and allogeneic
                      applicability, these findings position CAR-CIK cells as
                      promising immune effectors for solid tumors.},
      keywords     = {Humans / Rhabdomyosarcoma: therapy / Rhabdomyosarcoma:
                      immunology / Cytokine-Induced Killer Cells: immunology /
                      Immunotherapy, Adoptive: methods / Animals / Receptor,
                      ErbB-2: immunology / Receptors, Chimeric Antigen: immunology
                      / Receptors, Chimeric Antigen: genetics / Receptors,
                      Chimeric Antigen: metabolism / Mice / Cell Line, Tumor /
                      Xenograft Model Antitumor Assays / Cytokines: metabolism /
                      Cytotoxicity, Immunologic / Benchmarking / CAR-T (Other) /
                      ERBB2 (Other) / cytokine-induced killer cells (CIK) (Other)
                      / rhabdomyosarcoma (Other) / solid tumors (Other) /
                      Receptor, ErbB-2 (NLM Chemicals) / Receptors, Chimeric
                      Antigen (NLM Chemicals) / ERBB2 protein, human (NLM
                      Chemicals) / Cytokines (NLM Chemicals)},
      cin          = {FM01},
      ddc          = {610},
      cid          = {I:(DE-He78)FM01-20160331},
      pnm          = {899 - ohne Topic (POF4-899)},
      pid          = {G:(DE-HGF)POF4-899},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:39963129},
      pmc          = {pmc:PMC11831232},
      doi          = {10.3389/fimmu.2025.1485817},
      url          = {https://inrepo02.dkfz.de/record/298948},
}