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

Abstract

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 <i>in vivo</i> 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 <i>in vivo</i> 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.