SSTR2 as an anatomical imaging marker and a safety switch to monitor and manage CAR T cell toxicity. Academic Article uri icon

Overview

abstract

  • 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.

publication date

  • December 3, 2022

Research

keywords

  • Immunotoxins
  • T-Lymphocytes

Identity

PubMed Central ID

  • PMC9719480

Scopus Document Identifier

  • 85143234061

Digital Object Identifier (DOI)

  • 10.1073/pnas.101130498

PubMed ID

  • 36463361

Additional Document Info

volume

  • 12

issue

  • 1