RT Journal Article
SR Electronic
T1 Antigen-Dependent Inducible T-Cell Reporter System for PET Imaging of Breast Cancer and Glioblastoma
JF Journal of Nuclear Medicine
JO J Nucl Med
FD Society of Nuclear Medicine
SP 137
OP 144
DO 10.2967/jnumed.122.264284
VO 64
IS 1
A1 Jaehoon Shin
A1 Matthew F.L. Parker
A1 Iowis Zhu
A1 Aryn Alanizi
A1 Carlos I. Rodriguez
A1 Raymond Liu
A1 Payal B. Watchmaker
A1 Mausam Kalita
A1 Joseph Blecha
A1 Justin Luu
A1 Brian Wright
A1 Suzanne E. Lapi
A1 Robert R. Flavell
A1 Hideho Okada
A1 Thea D. Tlsty
A1 Kole T. Roybal
A1 David M. Wilson
YR 2023
UL http://jnm.snmjournals.org/content/64/1/137.abstract
AB For the past several decades, chimeric antigen receptor T-cell therapies have shown promise in the treatment of cancers. These treatments would greatly benefit from companion imaging biomarkers to follow the trafficking of T cells in vivo. Methods: Using synthetic biology, we engineered T cells with a chimeric receptor synthetic intramembrane proteolysis receptor (SNIPR) that induces overexpression of an exogenous reporter gene cassette on recognition of specific tumor markers. We then applied a SNIPR-based PET reporter system to 2 cancer-relevant antigens, human epidermal growth factor receptor 2 (HER2) and epidermal growth factor receptor variant III (EGFRvIII), commonly expressed in breast and glial tumors, respectively. Results: Antigen-specific reporter induction of the SNIPR PET T cells was confirmed in vitro using green fluorescent protein fluorescence, luciferase luminescence, and the HSV-TK PET reporter with 9-(4-18F-fluoro-3-[hydroxymethyl]butyl)guanine ([18F]FHBG). T cells associated with their target antigens were successfully imaged using PET in dual-xenograft HER2+/HER2− and EGFRvIII+/EGFRvIII− animal models, with more than 10-fold higher [18F]FHBG signals seen in antigen-expressing tumors versus the corresponding controls. Conclusion: The main innovation found in this work was PET detection of T cells via specific antigen-induced signals, in contrast to reporter systems relying on constitutive gene expression.