Imaging strategies for CAR T-cell immunotherapy of solid tumors

The unprecedented efficacy of chimeric antigen receptor (CAR) T-cell immunotherapy of CD19+ B-cell malignancy has paved the way for its establishment as a new therapeutic pillar of hematologic oncology. Nonetheless, formidable obstacles hinder the attainment of comparable success in patients with solid tumors. To accelerate progress and rapidly characterize emerging toxicities, systems that permit the repeated and noninvasive assessment of CAR T-cell bio-distribution would be invaluable. In this presentation, we describe our experience with two clinically applicable strategies to achieve this. Following passive labelling with Indium 111, CAR T-cells can be tracked for up to 96 hours in cancer-bearing hosts using SPECT-CT imaging, an approach that highlights the distinctive pattern of migration of these cells following intravenous or regional delivery routes. To extend imaging capability beyond this timeframe, we have co-expressed the human sodium iodide symporter (hNIS) in CAR-engineered T-cells. This symporter promotes the selective uptake of a number of clinically useful PET or SPECT tracer isotopes, enabling the long-term and repeated quantitative monitoring of the distribution of these cells in vivo. Together, these systems provide a clinically compliant toolkit for serial imaging of CAR T-cells, facilitating the improved understanding and further clinical development of this emerging therapeutic modality.