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- Title
Construction of truncated PSMA as a PET reporter gene for CAR T cell trafficking.
- Authors
Zhang, Yirui; Song, Xiangming; Xu, Zhuoshuo; Lv, Xiaoying; Long, Yu; Lan, Xiaoli; Lei, Ping
- Abstract
In solid tumors, there are multiple barriers for a chimeric antigen receptor (CAR) T cell to surmount in order to reach the tumor site. For better understanding whether CAR T cells effectively infiltrate into tumor site, and simultaneously, whether there are off-target effects, real-time monitoring technologies need to be established. Cell-based positron emission tomography reporter genes have been developed to monitor engineered cells in living subjects. In this study, we reported the construction of a novel reporter gene truncated prostate-specific membrane antigen (ΔPSMA) pending for monitoring CAR T cells using 68Ga-PSMA-617 and a method for tracking the distribution of CAR T cells in vivo was developed. Data were provided to demonstrate that ΔPSMA was predominantly localized on the plasma membrane and could take up 68Ga-PSMA-617 in vitro in a time-dependent manner. And the expression of ΔPSMA did not affect CAR expression and cytolytic capacity of CAR T cells. CAR-ΔPSMA T cell xenografts in nude mice were clearly imaged by positron emission tomography 60 min after injection of 68Ga-PSMA-617. PSMA paired with 68Ga-PSMA-617 was capable of identifying approximately 1 × 104 engineered CAR T cells. The ability to image small numbers of CAR T cells in vivo would be helpful to accelerate the translation of cell-based therapies into the clinic, and it may reinforce our understanding of treatment success, failure, and toxicity.
- Subjects
T cells; REPORTER genes; POSITRON emission tomography; CHIMERIC antigen receptors
- Publication
Journal of Leukocyte Biology, 2024, Vol 115, Issue 3, p476
- ISSN
0741-5400
- Publication type
Article
- DOI
10.1093/jleuko/qiad127