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Mall, S.* ; Yusufi, N.* ; Wagner, R.* ; Klar, R.* ; Bianchi, H.* ; Steiger, K.* ; Straub, M.* ; Audehm, S.* ; Laitinen, I.* ; Aichler, M. ; Peschel, C.* ; Ziegler, S.* ; Mustafa, M.* ; Schwaiger, M.* ; D'Alessandria, C.* ; Krackhardt, A.M.

Immuno-PET imaging of engineered human T cells in tumors.

Cancer Res. 76, 4113-4123 (2016)

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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.

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