Immuno-PET Imaging of Engineered Human T Cells in Tumors

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-t...

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Published in:Cancer research (Chicago, Ill.) Ill.), 2016-07, Vol.76 (14), p.4113-4123
Main Authors: Mall, Sabine, Yusufi, Nahid, Wagner, Ricarda, Klar, Richard, Bianchi, Henrique, Steiger, Katja, Straub, Melanie, Audehm, Stefan, Laitinen, Iina, Aichler, Michaela, Peschel, Christian, Ziegler, Sibylle, Mustafa, Mona, Schwaiger, Markus, D'Alessandria, Calogero, Krackhardt, Angela M
Format: Article
Language:English
Subjects:
Animals
Cell Line, Tumor
Gene Transfer Techniques
Humans
Immunologic Memory
Immunotherapy, Adoptive
Mice
Neoplasms - diagnostic imaging
Neoplasms - immunology
Positron Emission Tomography Computed Tomography - methods
Receptors, Antigen, T-Cell - genetics
T-Lymphocytes - immunology
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Summary: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 ((89)Zr)-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.
ISSN:0008-5472
1538-7445
DOI:10.1158/0008-5472.CAN-15-2784