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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)
Publ. Version/Full Text Supplement DOI PMC
Open Access Green as soon as Postprint is submitted to ZB.
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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Publication type Article: Journal article
Document type Scientific Article
Corresponding Author
Keywords Positron-emission-tomography; Metastatic Prostate-cancer; In-vivo Tracking; Monoclonal-antibody; Antileukemic Reactivity; Noninvasive Detection; Gene-therapy; Receptor; Lymphocytes; Antigen
ISSN (print) / ISBN 0008-5472
e-ISSN 1538-7445
Journal Cancer Research
Quellenangaben Volume: 76, Issue: 14, Pages: 4113-4123 Article Number: , Supplement: ,
Publisher American Association for Cancer Research (AACR)
Publishing Place Philadelphia, Pa.
Non-patent literature Publications
Reviewing status Peer reviewed
Institute(s) CCG Antigen-specific Immunotherapy (VIRO-KVA)
Institute of Pathology (PATH)
Research Unit Analytical Pathology (AAP)