SSTR2 as an anatomical imaging marker and a safety switch to monitor and manage CAR T cell toxicity
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...
| Main Authors: | , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Nature Portfolio
2022-12-01
|
| Series: | Scientific Reports |
| Online Access: | https://doi.org/10.1038/s41598-022-25224-z |
| _version_ | 1811190332737454080 |
|---|---|
| author | Yago Alcaina Yanping Yang Yogindra Vedvyas Jaclyn E. McCloskey Moonsoo M. Jin |
| author_facet | Yago Alcaina Yanping Yang Yogindra Vedvyas Jaclyn E. McCloskey Moonsoo M. Jin |
| author_sort | Yago Alcaina |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-04-11T14:48:28Z |
| format | Article |
| id | doaj.art-b4d931c057124558b1311f10901b0857 |
| institution | Directory Open Access Journal |
| issn | 2045-2322 |
| language | English |
| last_indexed | 2024-04-11T14:48:28Z |
| publishDate | 2022-12-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj.art-b4d931c057124558b1311f10901b08572022-12-22T04:17:33ZengNature PortfolioScientific Reports2045-23222022-12-0112111210.1038/s41598-022-25224-zSSTR2 as an anatomical imaging marker and a safety switch to monitor and manage CAR T cell toxicityYago Alcaina0Yanping Yang1Yogindra Vedvyas2Jaclyn E. McCloskey3Moonsoo M. Jin4Molecular Imaging Innovations Institute, Department of Radiology, Weill Cornell MedicineMolecular Imaging Innovations Institute, Department of Radiology, Weill Cornell MedicineMolecular Imaging Innovations Institute, Department of Radiology, Weill Cornell MedicineMolecular Imaging Innovations Institute, Department of Radiology, Weill Cornell MedicineMolecular Imaging Innovations Institute, Department of Radiology, Weill Cornell MedicineAbstract 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.https://doi.org/10.1038/s41598-022-25224-z |
| spellingShingle | Yago Alcaina Yanping Yang Yogindra Vedvyas Jaclyn E. McCloskey Moonsoo M. Jin SSTR2 as an anatomical imaging marker and a safety switch to monitor and manage CAR T cell toxicity Scientific Reports |
| title | SSTR2 as an anatomical imaging marker and a safety switch to monitor and manage CAR T cell toxicity |
| title_full | SSTR2 as an anatomical imaging marker and a safety switch to monitor and manage CAR T cell toxicity |
| title_fullStr | SSTR2 as an anatomical imaging marker and a safety switch to monitor and manage CAR T cell toxicity |
| title_full_unstemmed | SSTR2 as an anatomical imaging marker and a safety switch to monitor and manage CAR T cell toxicity |
| title_short | SSTR2 as an anatomical imaging marker and a safety switch to monitor and manage CAR T cell toxicity |
| title_sort | sstr2 as an anatomical imaging marker and a safety switch to monitor and manage car t cell toxicity |
| url | https://doi.org/10.1038/s41598-022-25224-z |
| work_keys_str_mv | AT yagoalcaina sstr2asananatomicalimagingmarkerandasafetyswitchtomonitorandmanagecartcelltoxicity AT yanpingyang sstr2asananatomicalimagingmarkerandasafetyswitchtomonitorandmanagecartcelltoxicity AT yogindravedvyas sstr2asananatomicalimagingmarkerandasafetyswitchtomonitorandmanagecartcelltoxicity AT jaclynemccloskey sstr2asananatomicalimagingmarkerandasafetyswitchtomonitorandmanagecartcelltoxicity AT moonsoomjin sstr2asananatomicalimagingmarkerandasafetyswitchtomonitorandmanagecartcelltoxicity |