Reporter gene imaging of targeted T cell immunotherapy in recurrent glioma

Sci Transl Med. 2017 Jan 18;9(373):eaag2196. doi: 10.1126/scitranslmed.aag2196.

Abstract

High-grade gliomas are aggressive cancers that often become rapidly fatal. Immunotherapy using CD8+ cytotoxic T lymphocytes (CTLs), engineered to express both herpes simplex virus type 1 thymidine kinase (HSV1-TK) and interleukin-13 (IL-13) zetakine chimeric antigen receptor (CAR), is a treatment strategy with considerable potential. To optimize this and related immunotherapies, it would be helpful to monitor CTL viability and trafficking to glioma cells. We show that noninvasive positron emission tomography (PET) imaging with 9-[4-[18F]fluoro-3-(hydroxymethyl)butyl]guanine ([18F]FHBG) can track HSV1-tk reporter gene expression present in CAR-engineered CTLs. [18F]FHBG imaging was safe and enabled the longitudinal imaging of T cells stably transfected with a PET reporter gene in patients. Further optimization of this imaging approach for monitoring in vivo cell trafficking should greatly benefit various cell-based therapies for cancer.

Publication types

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

MeSH terms

  • Aged
  • Brain Neoplasms / diagnostic imaging*
  • Brain Neoplasms / therapy
  • Female
  • Gene Expression
  • Genes, Reporter*
  • Genetic Therapy / methods
  • Glioma / diagnostic imaging*
  • Glioma / therapy
  • Humans
  • Immunotherapy / methods*
  • Interleukin-13 / metabolism
  • Male
  • Middle Aged
  • Neoplasm Recurrence, Local
  • Positron-Emission Tomography
  • Prospective Studies
  • Receptors, Antigen, T-Cell / metabolism*
  • T-Lymphocytes, Cytotoxic / cytology*
  • Thymidine Kinase / metabolism

Substances

  • Interleukin-13
  • Receptors, Antigen, T-Cell
  • interleukin-13, human
  • Thymidine Kinase