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Safety switches for adoptive cell therapy.

Ali Can Sahillioglu1, Ton N Schumacher1

  • 1Division of Molecular Oncology & Immunology, Oncode Institute, The Netherlands Cancer Institute, Amsterdam, The Netherlands.

Current Opinion in Immunology
|August 14, 2021
PubMed
Summary

Genetic safety switches for adoptive T cell therapy offer reversible control to mitigate severe toxicities. These systems enhance cancer treatment safety by managing T cell activity in vivo.

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Area of Science:

  • Immunology
  • Cell Therapy
  • Cancer Research

Background:

  • Adoptive T cell therapies, including CAR-T and TCR-T cells, show potent anti-cancer activity but carry risks of severe toxicities.
  • Managing these toxicities necessitates developing controllable T cell therapies with safety mechanisms.
  • Genetic safety switches are crucial for in vivo control of engineered T cells.

Purpose of the Study:

  • To review the mechanistic classes of genetic safety switches for adoptive T cell therapy.
  • To discuss the advantages and limitations of various T cell control technologies.
  • To highlight advancements in reversible control of T cell products.

Main Methods:

  • Review of existing literature on genetic safety switches for T cell therapy.
  • Categorization of safety switches based on their control mechanisms (transcription-based, protein-based, etc.).
  • Analysis of control strategies including small molecules, protein regulators, and physical stimuli.

Main Results:

  • Various genetic safety switches enable reversible control of T cell activity.
  • Technologies include transcription-based and protein-based antigen receptor control, split receptors, and small molecule-responsive antibodies.
  • Physical stimuli like light, ultrasound, and heat offer alternative control modalities.

Conclusions:

  • Genetic safety switches are essential for enhancing the safety profile of adoptive T cell therapies.
  • Reversible control mechanisms allow for fine-tuning T cell activity and mitigating adverse effects.
  • Further development of these switches is critical for broader clinical application of T cell-based cancer treatments.