%0 Journal Article
%A Moser, Laura M
%A Heim, Catrin
%A Koschade, Sebastian E
%A Wendel, Philipp
%A Bozkurt, Süleyman
%A Harenkamp, Sabine
%A Kreyenberg, Hermann
%A Merker, Michael
%A Münch, Christian
%A Gradhand, Elise
%A Vogler, Meike
%A Ullrich, Evelyn
%A Bönig, Halvard
%A Klusmann, Jan-Henning
%A Bader, Peter
%A Wels, Winfried S
%A Rettinger, Eva
%T CAR-CIK vs. CAR-T: benchmarking novel cytokine-induced killer cells as solid tumor immunotherapy in ErbB2+ rhabdomyosarcoma.
%J Frontiers in immunology
%V 16
%@ 1664-3224
%C Lausanne
%I Frontiers Media
%M DKFZ-2025-00382
%P 1485817
%D 2025
%X 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.
%K Humans
%K Rhabdomyosarcoma: therapy
%K Rhabdomyosarcoma: immunology
%K Cytokine-Induced Killer Cells: immunology
%K Immunotherapy, Adoptive: methods
%K Animals
%K Receptor, ErbB-2: immunology
%K Receptors, Chimeric Antigen: immunology
%K Receptors, Chimeric Antigen: genetics
%K Receptors, Chimeric Antigen: metabolism
%K Mice
%K Cell Line, Tumor
%K Xenograft Model Antitumor Assays
%K Cytokines: metabolism
%K Cytotoxicity, Immunologic
%K Benchmarking
%K CAR-T (Other)
%K ERBB2 (Other)
%K cytokine-induced killer cells (CIK) (Other)
%K rhabdomyosarcoma (Other)
%K solid tumors (Other)
%K Receptor, ErbB-2 (NLM Chemicals)
%K Receptors, Chimeric Antigen (NLM Chemicals)
%K ERBB2 protein, human (NLM Chemicals)
%K Cytokines (NLM Chemicals)
%F PUB:(DE-HGF)16
%9 Journal Article
%$ pmid:39963129
%2 pmc:PMC11831232
%R 10.3389/fimmu.2025.1485817
%U https://inrepo02.dkfz.de/record/298948