Membrane‐Bound Multimodal Plasmonic Transducers for Noninvasive, In Situ Monitoring and Control of CAR T Cells Against Heterogeneous Solid Tumors
Abstract
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.
Article Details
Authors (15)
Myeongsoo Kim
Petit Institute for Bioengineering and Bioscience Georgia Institute of Technology Atlanta Georgia USA
Ali Zamat
Wallace H. Coulter Department of Biomedical Engineering Georgia Institute of Technology and Emory University School of Medicine Atlanta Georgia USA
Melissa Cadena
Wallace H. Coulter Department of Biomedical Engineering Georgia Institute of Technology and Emory University School of Medicine Atlanta Georgia USA
Chloé Thiveaud
Wallace H. Coulter Department of Biomedical Engineering Georgia Institute of Technology and Emory University School of Medicine Atlanta Georgia USA
Riya Sen
Wallace H. Coulter Department of Biomedical Engineering Georgia Institute of Technology and Emory University School of Medicine Atlanta Georgia USA
Jeungyoon Lee
Wallace H. Coulter Department of Biomedical Engineering Georgia Institute of Technology and Emory University School of Medicine Atlanta Georgia USA
Elif Kulaksizoglu
Wallace H. Coulter Department of Biomedical Engineering Georgia Institute of Technology and Emory University School of Medicine Atlanta Georgia USA
S. Abbey Oliver
Wallace H. Coulter Department of Biomedical Engineering Georgia Institute of Technology and Emory University School of Medicine Atlanta Georgia USA
Don VanderLaan
Wallace H. Coulter Department of Biomedical Engineering Georgia Institute of Technology and Emory University School of Medicine Atlanta Georgia USA
Sydney Fábrega
Wallace H. Coulter Department of Biomedical Engineering Georgia Institute of Technology and Emory University School of Medicine Atlanta Georgia USA
Zizhen Zha
Wallace H. Coulter Department of Biomedical Engineering Georgia Institute of Technology and Emory University School of Medicine Atlanta Georgia USA
Kelsey P. Kubelick
Jinhwan Kim
Department of Biomedical Engineering University of California Davis Davis California USA
Gabriel A. Kwong
Petit Institute for Bioengineering and Bioscience Georgia Institute of Technology Atlanta Georgia USA
Stanislav Y. Emelianov
Petit Institute for Bioengineering and Bioscience Georgia Institute of Technology Atlanta Georgia USA