SSTR2 as an anatomical imaging marker and a safety switch to monitor and manage CAR T cell toxicity

The ability to image adoptively transferred T cells in the body and to eliminate them to avoid toxicity will be vital for chimeric antigen receptor (CAR) T cell therapy, particularly against solid tumors with higher risk of off-tumor toxicity. Previously, we have demonstrated the utility of somatostatin receptor 2 (SSTR2) for CAR T cell imaging, illustrating the expansion and contraction of CAR T cells in tumor as well as off-tumor expansion. Using intercellular adhesion molecule 1-specific CAR T cells that secrete interleukin 12 (IL-12) as a model, herein we examined the potential of SSTR2 as a safety switch when combined with the SSTR2-specific maytansine-octreotate conjugate PEN-221. After rapid elimination of tumors, constitutive secretion of IL-12 led to continuous expansion of CAR T cells, causing systemic toxicity and elevated graft-versus-host disease (GvHD). Treatment with PEN-221 rapidly reduced the abundance of CAR T cells, decreasing the severity of toxicity and GvHD, and led to elongated survival. Our study supports the development of SSTR2 as a single genetic marker for CAR T cells that is readily applicable to humans both for anatomical detection of T cell distribution and an image-guided safety switch for rapid elimination of CAR T cells.