American Association for Cancer Research
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Supplementary Figure S2 from Immuno-PET Imaging of Engineered Human T Cells in Tumors

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posted on 2023-03-30, 23:32 authored by Sabine Mall, Nahid Yusufi, Ricarda Wagner, Richard Klar, Henrique Bianchi, Katja Steiger, Melanie Straub, Stefan Audehm, Iina Laitinen, Michaela Aichler, Christian Peschel, Sibylle Ziegler, Mona Mustafa, Markus Schwaiger, Calogero D'Alessandria, Angela M. Krackhardt

Investigation of different imaging time points to track TCR-transduced TCM after injection of 89Zr-aTCRmu-F(ab')2


Deutsche Forschungsgemeinschaft



Sensitive in vivo imaging technologies applicable to the clinical setting are still lacking for adoptive T-cell–based immunotherapies, an important gap to fill if mechanisms of tumor rejection or escape are to be understood. Here, we propose a highly sensitive imaging technology to track human TCR-transgenic T cells in vivo by directly targeting the murinized constant TCR beta domain (TCRmu) with a zirconium-89 (89Zr)-labeled anti–TCRmu-F(ab')2 fragment. Binding of the labeled or unlabeled F(ab')2 fragment did not impair functionality of transgenic T cells in vitro and in vivo. Using a murine xenograft model of human myeloid sarcoma, we monitored by Immuno-PET imaging human central memory T cells (TCM), which were transgenic for a myeloid peroxidase (MPO)–specific TCR. Diverse T-cell distribution patterns were detected by PET/CT imaging, depending on the tumor size and rejection phase. Results were confirmed by IHC and semiquantitative evaluation of T-cell infiltration within the tumor corresponding to the PET/CT images. Overall, these findings offer a preclinical proof of concept for an imaging approach that is readily tractable for clinical translation. Cancer Res; 76(14); 4113–23. ©2016 AACR.