Abstract
Although chimeric antigen receptor T (CART)-cell therapy has been successful in treating certain hematologic malignancies, wider adoption of CART-cell therapy is limited because of minimal activity in solid tumors and development of life-threatening toxicities, including cytokine release syndrome (CRS).There is a lack of a robust, clinically relevant imaging platform to monitor in vivo expansion and trafficking to tumor sites.To address this, we utilized the sodium iodide symporter (NIS) as a platform to image and track CART cells.We engineered CD19-directed and B-cell maturation antigen (BCMA)-directed CART cells to express NIS (NISCART19 and NISBCMA-CART, respectively) and tested the sensitivity of 18F-TFB-PET to detect trafficking and expansion in systemic and localized tumor models and in a CART-cell toxicity model.NISCART19 and NISBCMA-CART cells were generated through dual transduction with two vectors and demonstrated exclusive 125I uptake in vitro.18F-TFB-PET detected NISCART cells in vivo to a sensitivity level of 40,000 cells.18F-TFB-PET confirmed NISBCMA-CART-cell trafficking to the tumor sites in localized and systemic tumor models.In a xenograft model for CART-cell toxicity, 18F-TFB-PET revealed significant systemic uptake, correlating with CART-cell in vivo expansion, cytokine production, and development of CRS-associated clinical symptoms.NIS provides a sensitive, clinically applicable platform for CARTcell imaging with PET scan.18F-TFB-PET detected CART-cell trafficking to tumor sites and in vivo expansion, correlating with the development of clinical and laboratory markers of CRS.These studies demonstrate a noninvasive, clinically relevant method to assess CART-cell functions in vivo.
Original language | English (US) |
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Pages (from-to) | 1035-1046 |
Number of pages | 12 |
Journal | Cancer Immunology Research |
Volume | 9 |
Issue number | 9 |
DOIs | |
State | Published - Sep 2021 |
ASJC Scopus subject areas
- General Medicine