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- Title
Serial in vivo imaging of the targeted migration of human HSV-TK-transduced antigen-specific lymphocytes.
- Authors
Koehne, Guenther; Doubrovin, Mikhail; Doubrovina, Ekaterina; Zanzonico, Pat; Gallardo, Humilidad F.; Ivanova, Anna; Balatoni, Julius; Teruya-Feldstein, Julie; Heller, Glenn; May, Chad; Ponomarev, Vladimir; Ruan, Shutian; Finn, Ronald; Blasberg, Ronald G.; Bornmann, William; Riviere, Isabelle; Sadelain, Michel; O'Reilly, Richard J.; Larson, Steven M.
- Abstract
New technologies are needed to characterize the migration, survival, and function of antigen-specific T cells in vivo. Here, we demonstrate that Epstein-Barr virus (EBV)-specific T cells transduced with vectors encoding herpes simplex virus-1 thymidine kinase (HSV-TK) selectively accumulate radiolabeled 2'-fluoro-2'-deoxy-1-B-D-arabinofuranosyl-5-iodouracil (FIAU). After adoptive transfer, HSV-TK+ T cells labeled in vitro or in vivo with [131I]FIAU or [124I]FIAU can be noninvasively tracked in SCID mice bearing human tumor xenografts by serial images obtained by scintigraphy or positron emission tomography (PET), respectively. These T cells selectively accumulate in EBV+ tumors expressing the T cells' restricting HLA allele but not in EBV- or HLA-mismatched tumors. The concentrations of transduced T cells detected in tumors and tissues are closely correlated with the concentrations of label retained at each site. Radiolabeled transduced T cells retain their capacity to eliminate targeted tumors selectively. This technique for imaging the migration of ex vivo-transduced antigen-specific T cells in vivo is informative, nontoxic, and potentially applicable to humans.
- Subjects
EPSTEIN-Barr virus; T cells; HERPES simplex virus
- Publication
Nature Biotechnology, 2003, Vol 21, Issue 4, p405
- ISSN
1087-0156
- Publication type
Article
- DOI
10.1038/nbt805