Loading of CAR‐T cells with magnetic nanoparticles for controlled targeting suppresses inflammatory cytokine release and switches tumor cell death mechanism

Pfister F, Carnell L, Löffler L, Boosz P, Schaft N, Dörrie J, Stein R, Lenz M, Spiecker E, Huber C, Haddadin S, Berking C, Alexiou C, Janko C (2025)

Publication Type: Journal article

Publication year: 2025

Journal

MedComm

Book Volume: 6

Issue: 1

DOI: 10.1002/mco2.70039

Abstract

Therapies against hematological malignancies using chimeric antigen receptors (CAR)-T cells have shown great potential; however, therapeutic success in solid tumors has been constrained due to limited tumor trafficking and infiltration, as well as the scarcity of cancer-specific solid tumor antigens. Therefore, the enrichment of tumor-antigen specific CAR-T cells in the desired region is critical for improving therapy efficacy and reducing systemic on-target/off-tumor side effects. Here, we functionalized human CAR-T cells with superparamagnetic iron oxide nanoparticles (SPIONs), making them magnetically controllable for site-directed targeting. SPION-loaded CAR-T cells maintained their specific cytolytic capacity against melanoma cells expressing the CAR-specific antigen chondroitin sulfate proteoglycan (CSPG4). Importantly, SPIONs suppressed cytokine release in the loaded CAR-T cells, shifting the cell death phenotype in the tumor cells from pyroptosis to apoptosis. Furthermore, SPION-loaded CAR-T cells could be enriched in a dynamic flow model through an external magnetic field and be detected in MRI. These results demonstrate that lytic cytotoxicity is retained after SPION-functionalization and provides a basis for future site-specific immunotherapies against solid tumors with reduced systemic adverse side effects.

Authors with CRIS profile

Felix Pfister Department of Otorhinolaryngology – Head and Neck Surgery (HNO-Klinik) Lucas Carnell Department of Otorhinolaryngology – Head and Neck Surgery (HNO-Klinik) Lisa Löffler Professur für Nanomedizin Philipp Boosz Department of Orthopaedic and Trauma Surgery Niels Schaft Department of Dermatology Jan Dörrie Department of Dermatology René Stein Department of Otorhinolaryngology – Head and Neck Surgery (HNO-Klinik) Malte Lenz Lehrstuhl für Werkstoffwissenschaften (Mikro- und Nanostrukturforschung) Erdmann Spiecker Lehrstuhl für Werkstoffwissenschaften (Mikro- und Nanostrukturforschung) Christian Huber Department of Otorhinolaryngology – Head and Neck Surgery (HNO-Klinik) Carola Berking Lehrstuhl für Haut- und Geschlechtskrankheiten Christoph Alexiou Professur für Nanomedizin Christina Janko Department of Otorhinolaryngology – Head and Neck Surgery (HNO-Klinik)

Additional Organisation(s)

Nanoanalysis and Electron Microscopy (CENEM) Interdisziplinäres Zentrum, Center for Nanoanalysis and Electron Microscopy (CENEM)

Involved external institutions

Technische Universität München (TUM) DE Germany (DE)

How to cite

APA:

Pfister, F., Carnell, L., Löffler, L., Boosz, P., Schaft, N., Dörrie, J.,... Janko, C. (2025). Loading of CAR‐T cells with magnetic nanoparticles for controlled targeting suppresses inflammatory cytokine release and switches tumor cell death mechanism. MedComm, 6. https://doi.org/10.1002/mco2.70039

MLA:

Pfister, Felix, et al. "Loading of CAR‐T cells with magnetic nanoparticles for controlled targeting suppresses inflammatory cytokine release and switches tumor cell death mechanism." MedComm 6 (2025).

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