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Suicide genes: monitoring cells in patients with a safety switch

Linda G Eissenberg1, Michael Rettig1, Farrokh Dehdashti2

  • 1Department of Internal Medicine, Washington University School of Medicine, St. Louis MO, USA.

Frontiers in Pharmacology
|November 22, 2014
PubMed

Insights

Suicide genes in clinical trials act as tumor lytic agents and safety switches. They also serve as non-invasive reporters for monitoring genetically modified cell therapies and patient safety, aiding early intervention.

Area of Science:

  • Oncology
  • Immunotherapy
  • Medical Imaging

Background:

  • Suicide gene therapy is increasingly integrated into clinical trials for cancer treatment and cell-based therapies.
  • These genes function both as direct tumor-lytic agents and as crucial safety mechanisms for genetically modified cell therapies.
  • Beyond safety, suicide genes offer non-invasive monitoring of therapeutic cell biodistribution and biological effects.

Purpose of the Study:

  • To explore the utility of suicide genes as non-invasive reporters in clinical trials.
  • To assess the potential of suicide gene imaging for monitoring cell therapy outcomes and patient safety.
  • To discuss challenges and future directions in suicide gene therapy and imaging.

Main Methods:

  • Utilized (18)F-9-(4-fluoro-3-hydroxymethylbutyl)guanine ((18)FHBG) and positron emission tomography/computed tomography (PET/CT) imaging.
  • Tracked T cells engineered with herpes simplex virus thymidine kinase (HSV-TK) in a clinical trial setting.
  • Correlated imaging data with preclinical findings to assess T cell migration and potential adverse events.

Main Results:

  • Demonstrated the application of PET/CT imaging with (18)FHBG to follow engineered T cells in patients.
  • Aimed to discern patterns of T cell migration indicative of early graft-versus-host disease development.
  • Identified current challenges including suicide gene selection, radiotracer biodistribution discrepancies between species, and detection thresholds.

Conclusions:

  • Suicide gene imaging provides a valuable tool for monitoring cell therapies and patient safety in clinical trials.
  • Further development of suicide genes and corresponding radiolabel probes is necessary for broader clinical application.
  • Optimizing imaging techniques and understanding biodistribution are key to realizing the full potential of this approach.
Keywords:
PET-imaginggene therapyregenerative medicinesuicide genethymidine kinasetransplant biology

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