Cell-based cancer immunotherapy holds potential as a therapeutic approach, yet its application for solid tumour treatment remains challenging. Here we report a focused-ultrasound-based approach that mechanically induces the localized expression of CD19 antigen within a subpopulation of cells within solid tumours, which function as local ‘training centres’ to activate chimeric antigen receptor T cells. Activated chimeric antigen receptor T cells attack the whole cancer cell population near the tumour site, thus achieving cancer suppression. The system achieves targeted gene expression by integrating focused-ultrasound-triggered mechanical stimulation and the subsequent calcium response of cancer cells with a doxycycline-gated AND-logic genetic circuit, both of which need to be active for effective induction of CD19 expression. We validate the functionality of the approach in vitro, in organoids and in vivo, achieving direct control of user-designed gene expressions through FUS-mediated mechanical stimulation without the need of any cofactor, demonstrating the approach’s potential as a versatile platform for precisely controllable immunotherapy. Overall, our combinatorial approach offers a focused-ultrasound-controlled remote and non-invasive priming of solid tumours for effective and safe chimeric antigen receptor T cell immunotherapy via the induced production of clinically validated antigens.

Functional ultrasound (fUS) flow imaging provides a non-invasive method for the in vivo study of cerebral blood flow and neural activity. This study used functional flow imaging to investigate rat brain’s response to ultrasound and colored-light stimuli. Male Long-Evan rats were exposed to direct full-field strobe flashes light and ultrasound stimulation to their retinas, while brain activity was measured using high-frequency ultrasound imaging. Our study found that light stimuli, particularly blue light, elicited strong responses in the visual cortex and lateral geniculate nucleus (LGN), as evidenced by changes in cerebral blood volume (CBV). In contrast, ultrasound stimulation elicited responses undetectable with fUS flow imaging, although these were observable when directly measuring the brain’s electrical signals. These findings suggest that fUS flow imaging can effectively differentiate neural responses to visual stimuli, with potential applications in understanding visual processing and developing new diagnostic tools.

Ultrasound can safely penetrate deep into biological tissues, which has allowed this modality to be extensively used in clinical applications including diagnostic imaging, thermal ablation and lithotripsy. Recent identification of ultrasound-sensitive molecular actuators has led to the development of sonogenetics, a new and rapidly growing field. Here, these actuators are expressed in target cells, sensitizing these cells to the mechanical and/or thermal bioeffects of ultrasound, allowing them to be selectively manipulated using non-invasive ultrasound stimulation with high spatial and temporal precision. In this review, we will outline current sonogenetic approaches to manipulate both neurons and immune cells in vitro and in vivo, along with some practical considerations associated with designing these studies. Additionally, we highlight some exciting ongoing avenues for research and provide perspectives on the future of sonogenetics in the lab and the clinic. We suggest that by combining cell type resolution with the non-invasive nature of ultrasound stimulation, sonogenetics has the potential to revolutionize both scientific research and clinical practice.

This webinar discusses what sono-mechanogenetics is and the application of this novel technology in oncology and beyond.