In Vivo Ultrasound and Photoacoustic Imaging of Nanoparticle-Engineered T Cells and Post-Treatment Assessment to Guide Adoptive Cell Immunotherapy

Despite great promise, adoptive cell therapy (ACT) continues to fail at treating a majority of cancers, especially solid tumors. To inform development and expedite the translation of more potent cellular immunotherapies, advanced immunoimaging tools are needed to better understand the in vivo requirements for generating a robust immune response. Even methods to evaluate the delivery, location, and status of transferred T cells at the tumor target are lacking. Therefore, a real-time, safe, noninvasive, longitudinal imaging method is critically needed to 1) monitor adoptive T cell location and status and 2) assess treatment progression and response through imaging biomarkers. Here, we developed a combined ultrasound (US) and photoacoustic (PA) imaging approach to enable T cell tracking following adoptive transfer for cancer immunotherapy. Our approach leverages highly photostable gold nanorods and cell surface engineering to tag the T cells without impacting effector functions, as well as generate PA contrast for imaging post-transfer. Our in vivo US/PA imaging approach detected nanoparticle-labeled T cell accumulation at the tumor, visualized changes in tumor volume, and conveyed accompanying changes in blood biomarkers. US/PA data also showed different trends according to a positive or negative antitumor response to T cell therapy over 7 days. Results highlight the potential of the approach and motivate future development to expand the platform for advanced, theranostic immunoimaging.