CD19 Chimeric Antigen Receptor T Cells From Patients With Chronic Lymphocytic Leukemia Display an Elevated IFN-γ Production Profile. Issue 2 (February 2018)

• Record Type: Journal Article
• Authors: Magalhaes, Isabelle; Kalland, Ingrid; Kochenderfer, James N.; Österborg, Anders; Uhlin, Michael; Mattsson, Jonas
• Is Part Of: Journal of immunotherapy. Volume 41:Issue 2(2018:Feb./Mar.)
• Publication Date: 2018-02
• Subjects: chimeric antigen receptor -- CD19 -- chronic lymphocytic leukemia -- T cell; Immunotherapy -- Periodicals; Immunotherapy -- Periodicals; Neoplasms -- therapy -- Periodicals; Electronic journals; Electronic journals; 615.37
• DOI: 10.1097/CJI.0000000000000193
• Languages: English
• ISSNs: 1524-9557

Abstract

Abstract : CD19 chimeric antigen receptor (CAR) T cell immunotherapy has demonstrated dramatic results for the treatment of B cell malignancies such as chronic lymphocytic leukemia (CLL). As T cell defects are common in patients with CLL, we compared the T cells from these patients with healthy donors (HDs), and subsequently the CD19 CAR T cells produced from patients and HDs. Despite initial differences when comparing the phenotype of circulating T cells in patients with CLL and HDs, the CD19 CAR T cells manufactured from patients' or HDs' cells showed a similar phenotype (effector memory or terminally differentiated), both were specifically activated by and killed CD19 + target cells, and secreted cytokines (ie, IL-2, TNF, and IFN-γ). The frequency of CD19 CAR T cells producing IFN-γ was significantly higher in cells produced from patients as compared with those produced from HDs. Furthermore, our data showed that the polyfunctional profile of CD19 CAR + T cells was differently modulated by CD19 + K562 cells and autologous B cells. The increased IFN-γ production by CD19 CAR T cells produced from patients with CLL after in vitro stimulation, may if this is also the case in vivo, contribute to a higher risk of a cytokine release syndrome in patients. The different impact by CD19 + target cells on the polyfunctional profile of CD19 CAR T cells in vitro underlines the importance of the choice of CD19 + target cells when assessing CD19 CAR T cells functions. Abstract : Supplemental Digital Content is available in the text.