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Thermal sonogenetics for adoptive cell transfer therapy.

Ana Baez1, Kyle Hazel1, Zakary Guertin1

  • 1Department of Biology, Concordia University, Montreal H4B 1R6, Canada.

Journal of Controlled Release : Official Journal of the Controlled Release Society
|February 26, 2026
PubMed
Summary
This summary is machine-generated.

Focused ultrasound (FUS) enables precise control of engineered immune cells for cancer therapy. Thermal sonogenetics uses FUS to activate cells remotely, improving safety and efficacy of adoptive cell transfer (ACT).

Keywords:
AcousticsCAR-T cellsFocused ultrasoundHigh intensity focused ultrasoundImmunotherapyTargeted therapy

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Area of Science:

  • Immunotherapy
  • Biotechnology
  • Oncology

Background:

  • Adoptive cell transfer (ACT) shows promise in cancer treatment but faces challenges like toxicity and tumor microenvironment suppression.
  • Current inducible gene circuit systems for ACT have limitations in clinical translation due to pharmacokinetics and tissue penetration.
  • Focused ultrasound (FUS) offers a non-invasive method for localized deep tissue activation.

Purpose of the Study:

  • To review advances in FUS-mediated, heat-inducible genetic control for ACT-based immunotherapy.
  • To discuss the limitations of current ACT platforms and the need for controllable systems.
  • To explore the potential of thermal sonogenetics for precise and reversible control of engineered immune cells.

Main Methods:

  • Review of current ACT platforms (TIL, TCR-T, CAR-T) and their limitations.
  • Discussion of heat shock promoters (HSP70) as thermal gene switches.
  • Summary of preclinical studies using FUS for inducible gene expression in various cell types.

Main Results:

  • FUS enables localized and deep tissue heating for precise activation of genetically engineered cells.
  • Heat-inducible promoters, particularly HSP70 elements, are key components of thermal gene switches.
  • Preclinical studies demonstrate the feasibility of FUS-mediated inducible gene expression.

Conclusions:

  • Thermal sonogenetics offers a promising strategy for remote, precise, and reversible control of engineered immune cells.
  • This approach has the potential to enhance the safety and efficacy of ACT-based immunotherapies.
  • Further research is needed to address limitations and advance clinical translation.