Adoptive cell therapy (ACT) continues to fail at treating solid tumors where only a small fraction of CAR T cells typically accumulates at the target. Furthermore, off-tumor toxicity remains a major challenge. Therefore, methods to evaluate cell trafficking, status, and mechanism of action in the context of morphological/functional changes at the primary tumor (and regional lymph nodes) are needed to plan and guide successful ACT. Here we present a comprehensive approach to guide ACT using photoacoustic (PA) and ultrasound (US) imaging and CAR T cells engineered with thermal gene switch (Miller et al. Nature BME, 2021) and tagged with nanoparticles (Kim et al. 2024).  Our in vivo studies showed that a synergistic combination of US/PA imaging and T cell surface engineering to tag cells with plasmonic nanoparticles enables the tracking of adoptive T cell infiltration in solid tumors. In addition, US/PA imaging of T cells tagged with photomagnetic nanoparticles confirmed the enhanced accumulation of cells in the primary tumor and regional lymph nodes. Furthermore, following cell infiltration, US/PA thermal imaging was developed and deployed to guide thermal gene switch CAR T cell activation using mild heat delivered by either continuous wave laser or focused ultrasound. Finally, US/PA imaging was used to assess ACT progression in vivo by analyzing imaging biomarkers. Our results indicate feasibility of the T cell tagging with NPs and US/PA imaging of adoptive T cells with clinically relevant spatial resolution and imaging depth thus providing critical imaging feedback to expedite development, translation, and expansion of ACT.

Dr. Stanislav (Stas) Emelianov started his research career at the University of Michigan. In 2002, Dr. Emelianov moved to the University of Texas at Austin where he established the Ultrasound Imaging and Therapeutics Research Laboratory. In 2015, Dr. Emelianov and his laboratory relocated to Georgia Tech and Emory University School of Medicine.

Throughout his career, Dr. Emelianov has pioneered several ultrasound-based imaging techniques including shear wave elasticity imaging, ultrasound-guided photoacoustic imaging, and molecular ultrasound/photoacoustic (US/PA) imaging using exogenous nanometer sized imaging contrast agents. In the course of his work, he has published more than 250 peer-reviewed papers, review articles, and book chapters. He is listed as (co)inventor on numerous patents and disclosures.

In recognition of his contributions to the field, Dr. Emelianov has been named a Fellow of the American Institute for Medical and Biological Engineering (AIMBE), Institute of Electrical and Electronics Engineers (IEEE), Acoustical Society of America (OSA), and Society of Photographic Instrumentation Engineers (SPIE).