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CD19 Chimeric Antigen Receptor T Cells From Patients With Chronic Lymphocytic Leukemia Display an Elevated IFN-γ Production Profile

Magalhaes, Isabelle*; Kalland, Ingrid*; Kochenderfer, James, N.; Österborg, Anders*,‡; Uhlin, Michael§,∥; Mattsson, Jonas*,¶

doi: 10.1097/CJI.0000000000000193
Basic Studies
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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.

*Department of Oncology-Pathology

§Department of Clinical Science, Division of Surgery, Intervention and Technology, Karolinska Institutet

Departments of Hematology

Clinical Immunology and Transfusion Medicine

Center for Allogeneic Stem Cell Transplantation, Karolinska University Hospital, Huddinge, Stockholm, Sweden

Experimental Transplantation and Immunology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD

Reprints: Isabelle Magalhaes, Department of Oncology-Pathology, Karolinska Institutet, F79 Karolinska University Hospital, Huddinge, Stockholm 141 86, Sweden (e-mail: isabelle.magalhaes@ki.se).

Received July 14, 2017

Accepted October 4, 2017

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