Scientific Reports
Scientific Reports
2 years ago

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

SSTR2 as an anatomical imaging marker and a safety switch to monitor and manage CAR T cell toxicity
Yago Alcaina, Yanping Yang, Yogindra Vedvyas, Jaclyn E. McCloskey, Moonsoo M. Jin
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 (ICAM-1)-specific CAR T cells that secrete interleukin (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. Constitutive secretion of IL-12 led to continuous expansion of CAR T cells after rapid elimination of tumors, causing systemic toxicity in mice with intact MHC expression. Treatment with PEN-221 rapidly reduced the abundance of CAR T cells, decreasing the severity of xenogeneic graft-versus-host disease (GvHD), and prolonged 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.

Publisher URL: https://www.nature.com/articles/s41598-022-25224-z

Open URL: https://www.nature.com/articles/s41598-022-25224-z.pdf

DOI: 10.1038/s41598-022-25224-z

Open access
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