Human T cells loaded with superparamagnetic iron oxide nanoparticles retain antigen-specific TCR functionality.

Pfister F, Dörrie J, Schaft N, Buchele V, Unterweger H, Carnell LR, Schreier P, Stein R, Kubánková M, Guck J, Hackstein H, Alexiou C, Janko C (2023)

Publication Type: Journal article

Publication year: 2023

Journal

Frontiers in Immunology Frontiers Research Foundation / Frontiers Media

Book Volume: 14

DOI: 10.3389/fimmu.2023.1223695

Abstract

BACKGROUND: Immunotherapy of cancer is an emerging field with the potential to improve long-term survival. Thus far, adoptive transfer of tumor-specific T cells represents an effective treatment option for tumors of the hematological system such as lymphoma, leukemia or myeloma. However, in solid tumors, treatment efficacy is low owing to the immunosuppressive microenvironment, on-target/off-tumor toxicity, limited extravasation out of the blood vessel, or ineffective trafficking of T cells into the tumor region. Superparamagnetic iron oxide nanoparticles (SPIONs) can make cells magnetically controllable for the site-specific enrichment. METHODS: In this study, we investigated the influence of SPION-loading on primary human T cells for the magnetically targeted adoptive T cell therapy. For this, we analyzed cellular mechanics and the T cell response after stimulation via an exogenous T cell receptor (TCR) specific for the melanoma antigen MelanA or the endogenous TCR specific for the cytomegalovirus antigen pp65 and compared them to T cells that had not received SPIONs. RESULTS: SPION-loading of human T cells showed no influence on cellular mechanics, therefore retaining their ability to deform to external pressure. Additionally, SPION-loading did not impair the T cell proliferation, expression of activation markers, cytokine secretion, and tumor cell killing after antigen-specific activation mediated by the TCR. CONCLUSION: In summary, we demonstrated that SPION-loading of T cells did not affect cellular mechanics or the functionality of the endogenous or an exogenous TCR, which allows future approaches using SPIONs for the magnetically enrichment of T cells in solid tumors.

Authors with CRIS profile

Felix Pfister Department of Otorhinolaryngology – Head and Neck Surgery Jan Dörrie Department of Dermatology Niels Schaft Department of Dermatology Vera Buchele Department of Transfusion Medicine and Haemostaseology Harald Unterweger Department of Otorhinolaryngology – Head and Neck Surgery Patrick Schreier Department of Medicine 1 – Gastroenterology, Pneumology and Endocrinology René Stein Department of Otorhinolaryngology – Head and Neck Surgery Jochen Guck
Holger Hackstein Professur für Transfusionsmedizin und Cell-Engineering Christoph Alexiou Professur für Nanomedizin Christina Janko Department of Otorhinolaryngology – Head and Neck Surgery

Involved external institutions

Max-Planck-Institut für die Physik des Lichts (MPL) / Max Planck Institute for the Science of Light DE Germany (DE)

How to cite

APA:

Pfister, F., Dörrie, J., Schaft, N., Buchele, V., Unterweger, H., Carnell, L.R.,... Janko, C. (2023). Human T cells loaded with superparamagnetic iron oxide nanoparticles retain antigen-specific TCR functionality. Frontiers in Immunology, 14. https://doi.org/10.3389/fimmu.2023.1223695

MLA:

Pfister, Felix, et al. "Human T cells loaded with superparamagnetic iron oxide nanoparticles retain antigen-specific TCR functionality." Frontiers in Immunology 14 (2023).

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