CAR-T-Zellen erkennen und eliminieren den Thyreotropin-Rezeptor exprimierende differenzierte Schilddrüsenkarzinomzellen

Hintergrund: Das differenzierte Schilddrüsenkarzinom weist eine sehr gute Prognose auf. Dennoch gibt es Patienten, die refraktär auf die bereits etablier-ten Therapiemöglichkeiten der operativen Therapie, der Radioiodtherapie und der dauerhaften Thyreotropin-Suppression reagieren. Chimäre Antigenrez...

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Bibliographic Details
Main Author: Spieker, Nicola
Contributors: Verburg, Frederik A. (Prof. Dr. Dr. med.) (Thesis advisor)
Format: Doctoral Thesis
Language:German
Published: Philipps-Universität Marburg 2020
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Table of Contents: Background: Differenciated thyroid cancer presents with a very favourable prognosis. However, there are some cases with differentiated thyroid cancer that are refractory to the established treatment consistant of thyroidectomy, radioactive 131-Iodide therapy and Thyrotropin-suppression. Chimeric antigen receptor T-cells (CART) have already shown impressive results in hematological cancers. Objective: This study aims to evaluate the potential of CART targeting the Thyrotropin-receptor (anti-TSHR CART) against differentiated, TSHR-positive thyroid cancer. Material and methods: Target cells are the papillary thyroid cancer cell line K-1 and the follicular thyroid cancer cell line FTC-133. The killing of target cells by anti-TSHR CART is measured as a reduction of target cells in co-culture un-der the microscope, the fluorescence microscope (after GFP-labelling) and with a caspase-3/7-luminescnece analysis. Results: With K-1 cells we could detect a significant difference between anti-TSHR CART and unspecific CART (T-value = 0.01), while anti-TSHR CART in comparison to unmodified T cells just missed significance (T-value = 0.06). With FTC-133 cells we could detect a significant difference between anti-TSHR CART and unmodified T cells (T-value = 0.02), while anti-TSHR CART in com-parison to unspecific CART just missed significance (T-value = 0.06) (signifi-cance level α = 0.05). Conclusion: Anti-TSHR CART pose a potentially new treatment option to ab-late healthy and malignant transformed thyroid cells expressing the Thyrotropin-receptor.