Thermally Controlled State Switches for Engineered Macrophages

TL;DR

Researchers developed a thermal control system for macrophages that allows precise activation of gene expression in response to heat, enabling targeted immune responses.

Contribution

A novel thermal bioswitch was created to enable spatially controlled activation of macrophages in vivo.

Findings

A genetic circuit was designed to activate macrophages after a brief thermal stimulus.

In vivo activation using ultrasound heating resulted in localized gene expression lasting at least 14 days.

The thermal bioswitch enables stable transcriptional activation and secretion of IL-12 in macrophages.

Abstract

Advances in cellular immunotherapy promise new treatments
for conditions
such as cancer, autoimmune disease, and heart disease. While engineered
cells have the ability to recognize clinically relevant signals, traffic
to disease sites and interface with the host immune system, their
activity must be tightly controlled to minimize undesirable effects
in healthy tissues. One approach to obtaining specificity is to activate
the cells spatially using externally applied energy, such as ultrasound-delivered
heating. To facilitate such control, we designed and characterized
a genetic circuit that enables stable transcriptional activation of
macrophages after a brief thermal stimulus, resulting in the expression
of reporters or secretion of the cytokine IL-12. We demonstrate that in vivo activation of a mouse macrophage cell line containing
this bioswitch results in spatially localized gene expression for
at least 14 days after ultrasound heating. This thermal bioswitch
provides a precise control element for cell-therapeutic agents.

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