Citations 1
Development of a Clinically Relevant Reporter for Chimeric Antigen Receptor T-cell Expansion, Trafficking, and Toxicity
Bansal, Aditya , Siegler, Elizabeth L. , Yang, Nan , Khadka, Roman H., Newsom, Alysha N., Hansen, Michael J. , Cox, Michelle J. , Roman, Claudia Manriquez , Schick, Kendall J. , Can, İsmail , Tapper, Erin E. , Nevala, Wendy K. , Fonkoua, Lionel Aurelien Kankeu , Horvei, Paulina , Ruff, Michael W. , Pandey, Mukesh K. , DeGrado, Timothy R. , Suksanpaisan, Lukkana , Peng, Kah-Whye , Sakemura, Reona , Siegler, Elizabeth L , Cox, Michelle J , Manriquez Roman, Claudia , Schick, Kendall J , Can, Ismail , Adada, Mohamad M, Bezerra, Evandro D. , Kankeu Fonkoua, Lionel Aurelien, Parikh, Sameer A , Kay, Neil E , Kenderian, Saad S. , Pandey, Mukesh K , Hefazi, Mehrdad , Adada, Mohamad M , Parikh, Sameer A. , Kay, Neil E.
Cancer Immunology Research | July 9, 2021 | Volume: 9 | Issue: 9 | Pages: 1035-1046
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 (NIS+CART19 and NIS+BCMA-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. NIS+CART19 and NIS+BCMA-CART cells were generated through dual transduction with two vectors and demonstrated exclusive 125I uptake in vitro. 18F-TFB-PET detected NIS+CART cells in vivo to a sensitivity level of 40,000 cells. 18F-TFB-PET confirmed NIS+BCMA-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 CART-cell 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.