CAR-CIK vs. CAR-T: benchmarking novel cytokine-induced killer cells as solid tumor immunotherapy in ErbB2+ rhabdomyosarcoma
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Le résumé fourni par la source
Introduction 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). Methods 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. Results 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. Conclusion 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.
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Le contrôle bibliographique ouvert
DOI retrouvé dans Crossref DOI retrouvé ; titre concordant.
- Titre Crossref
- CAR-CIK vs. CAR-T: benchmarking novel cytokine-induced killer cells as solid tumor immunotherapy in ErbB2+ rhabdomyosarcoma
- Date Crossref
- 03/02/2025
- Éditeur
- Frontiers Media SA
- Type
- journal-article
Ce recoupement confirme des métadonnées liées au DOI. Il ne confirme ni la méthode ni les conclusions de l’étude, et il ne compte pas comme une seconde source scientifique indépendante.
Où se fait cette recherche
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Goethe University Frankfurt Department of Pediatrics pays non établi dans la noticeUniversité ou école supérieure
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Institute of Clinical Cancer Research pays non établi dans la noticeStructure de recherche
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Frankfurt Cancer Institute pays non établi dans la noticeOrganisation à but non lucratif
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Deutsches Konsortium für Translationale Krebsforschung pays non établi dans la noticeStructure de recherche
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Technische Universität Darmstadt pays non établi dans la noticeUniversité ou école supérieure
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Cardio-Pulmonary Institute pays non établi dans la noticeStructure de recherche
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University of Washington Department of Medicine pays non établi dans la noticeUniversité ou école supérieure
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Georg Speyer Haus pays non établi dans la noticeStructure de recherche
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German Cancer Consortium (DKTK) pays non établi dans la noticeInstitution
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Universitäres Centrum für Tumorerkrankungen (UCT) pays non établi dans la noticeInstitution
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Faculty of Medicine Institute of Biochemistry II pays non établi dans la noticeUniversité ou école supérieure
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Technical University of Darmstadt Institute for Organic Chemistry and Biochemistry pays non établi dans la noticeUniversité ou école supérieure
Department of Pediatrics — Goethe University Frankfurt, Institute of Clinical Cancer Research et Frankfurt Cancer Institute, avec 9 autres affiliations.
Une affiliation ne permet pas de déduire la nationalité d’un auteur.