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Membrane-Bound Multimodal Plasmonic Transducers for Noninvasive, In Situ Monitoring and Control of CAR T Cells
Myeongsoo Kim1,2,3, Ali Zamat2, Melissa Cadena2
1Petit Institute for Bioengineering and Bioscience, Georgia Institute of Technology, Atlanta, Georgia, USA.
Abstract:
Noninvasive monitoring and control of CAR T cells against heterogeneous solid tumors remain major challenges in understanding and improving treatment response. To address this, membrane-bound plasmonic transducers, composed of plasmonically coupled gold nanospheres in an anisotropic framework, were developed for multimodal photoacoustic imaging and localized thermal modulation of CAR T cell activity. These transducers exhibit approximately 90% absorption efficiency and photostability under laser fluences exceeding 20 mJ cm-2, delivering photoacoustic and thermal responses over multiple lasing cycles. Membrane-bound transducers on CAR T cells thus enable photoacoustic and thermal responsiveness upon laser excitation without compromising key cellular functions. In heterogeneous HER2-expressing breast tumor models, longitudinal photoacoustic imaging enabled prospective stratification of tumors based on early T cell trafficking, predicting responders versus nonresponders with high sensitivity and specificity. Moreover, transducer-mediated thermal modulation of intratumoral CAR T cells engineered with thermogenetic circuits to secrete T cell engagers redirected cytotoxicity toward antigen-negative tumors, overcoming antigen escape and consequently enhancing therapy. Taken together, we demonstrate a strategy to noninvasively monitor and control CAR T cells against heterogeneous solid tumors via membrane-bound multimodal transducers.
Insights
Researchers developed novel membrane-bound transducers for noninvasive monitoring and control of CAR T cells in solid tumors. This breakthrough enables early prediction of treatment response and enhanced therapy by overcoming antigen escape.
Area of Science:
- Biomedical Engineering
- Nanotechnology
- Immunotherapy
Background:
- Noninvasive monitoring and control of CAR T cells in solid tumors are critical for improving treatment efficacy.
- Heterogeneous tumors present challenges due to antigen escape and variable T cell responses.
Purpose of the Study:
- To develop a multimodal system for noninvasive monitoring and control of CAR T cells.
- To address challenges in treating heterogeneous solid tumors with CAR T cell therapy.
Main Methods:
- Development of membrane-bound plasmonic transducers (gold nanospheres in an anisotropic framework).
- Utilizing transducers for multimodal photoacoustic imaging and localized thermal modulation of CAR T cell activity.
- Employing HER2-expressing breast tumor models and CAR T cells engineered with thermogenetic circuits.
Main Results:
- Transducers demonstrated high absorption efficiency and photostability, enabling photoacoustic and thermal responses.
- Longitudinal photoacoustic imaging accurately stratified tumors and predicted treatment responders.
- Transducer-mediated thermal modulation redirected CAR T cell cytotoxicity, overcoming antigen-negative tumor escape.
Conclusions:
- Membrane-bound multimodal transducers offer a novel strategy for noninvasive monitoring and control of CAR T cells.
- This approach enhances CAR T cell therapy efficacy against heterogeneous solid tumors.
- The technology enables early prediction of treatment outcomes and overcomes antigen escape mechanisms.
