Imaging T Cell Dynamics and Function Using PET and Human Nuclear Reporter Genes

Methods Mol Biol. 2018:1790:165-180. doi: 10.1007/978-1-4939-7860-1_13.

Abstract

Adoptive cell transfer immunotherapy has demonstrated significant promise in the treatment of cancer, with long-term, durable responses. T cells expressing T cell receptors (TCRs) that recognize tumor antigens, or engineered with chimeric antigen receptors (CARs) can recognize and eliminate tumor cells even in advanced disease. Positron emission tomography (PET) imaging with nuclear reporter genes, a noninvasive method to track and monitor function of engineered cells in vivo, allows quantitative, longitudinal monitoring of these cells, including their expansion/contraction, migration, retention at target and off-target sites, and biological state. As an additional advantage, some reporter genes also exhibit "suicide potential" permitting the safe elimination of adoptively transferred T cells in instances of adverse reaction to therapy. Here, we describe the production of human nuclear reporter gene-expressing T cells and noninvasive PET imaging to monitor their cell fate in vivo.

Keywords: Chimeric antigen receptors; Human nuclear reporter gene; Immunotherapy; Nucleoside kinases; PET; Reporter probe; T cell.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adoptive Transfer
  • Animals
  • Arabinofuranosyluracil / analogs & derivatives
  • Genes, Reporter*
  • Humans
  • Mice
  • Mice, SCID
  • Molecular Imaging / methods*
  • Nuclear Proteins / metabolism
  • Positron-Emission Tomography / methods*
  • Receptors, Antigen, T-Cell / metabolism*
  • T-Lymphocytes / cytology*
  • T-Lymphocytes / immunology
  • T-Lymphocytes / metabolism

Substances

  • 2'-fluoro-2'-deoxy-5-fluoroethyl-1-beta-D-arabinofuranosyl uracil
  • Nuclear Proteins
  • Receptors, Antigen, T-Cell
  • Arabinofuranosyluracil