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Immuno-PET imaging of engineered human T cells in tumors.
Cancer Res. 76, 4113-4123 (2016)
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.
Impact Factor
Scopus SNIP
Web of Science
Times Cited
Times Cited
Scopus
Cited By
Cited By
Altmetric
8.556
1.921
36
42
Anmerkungen
Besondere Publikation
Auf Hompepage verbergern
Publikationstyp
Artikel: Journalartikel
Dokumenttyp
Wissenschaftlicher Artikel
Schlagwörter
Positron-emission-tomography; Metastatic Prostate-cancer; In-vivo Tracking; Monoclonal-antibody; Antileukemic Reactivity; Noninvasive Detection; Gene-therapy; Receptor; Lymphocytes; Antigen
Sprache
englisch
Veröffentlichungsjahr
2016
HGF-Berichtsjahr
2016
ISSN (print) / ISBN
0008-5472
e-ISSN
1538-7445
Zeitschrift
Cancer Research
Quellenangaben
Band: 76,
Heft: 14,
Seiten: 4113-4123
Verlag
American Association for Cancer Research (AACR)
Verlagsort
Philadelphia, Pa.
Begutachtungsstatus
Peer reviewed
Institut(e)
Institute of Virology (VIRO)
Institute of Pathology (PATH)
Research Unit Analytical Pathology (AAP)
Institute of Pathology (PATH)
Research Unit Analytical Pathology (AAP)
POF Topic(s)
30504 - Mechanisms of Genetic and Environmental Influences on Health and Disease
30205 - Bioengineering and Digital Health
30205 - Bioengineering and Digital Health
Forschungsfeld(er)
Immune Response and Infection
Enabling and Novel Technologies
Enabling and Novel Technologies
PSP-Element(e)
G-520100-001
G-500300-001
G-500390-001
G-500300-001
G-500390-001
WOS ID
WOS:000381111400010
Scopus ID
84978654959
PubMed ID
27354381
Erfassungsdatum
2016-07-05