Serial in vivo imaging of the targeted migration of human HSV-TK-transduced antigen-specific lymphocytes

G Koehne, M Doubrovin, E Doubrovina… - Nature …, 2003 - nature.com
G Koehne, M Doubrovin, E Doubrovina, P Zanzonico, HF Gallardo, A Ivanova, J Balatoni…
Nature biotechnology, 2003nature.com
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-β-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 …
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-β-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.
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