Open AccessCD19 Chimeric Antigen Receptor T Cells From Patients With Chronic Lymphocytic Leukemia Display an Elevated IFN-γ Production Profile
Author(s) -
Isabelle Magalhaes,
Ingrid Kalland,
James N. Kochenderfer,
Anders Österborg,
Michael Uhlin,
Jonas Mattsson
Publication year - 2018
Publication title -
journal of immunotherapy
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.805
H-Index - 92
eISSN - 1537-4513
pISSN - 1524-9557
DOI - 10.1097/cji.0000000000000193
Subject(s) - cd19 , chronic lymphocytic leukemia , chimeric antigen receptor , k562 cells , cytokine , antigen , immunology , interleukin 21 , t cell , immunotherapy , interleukin 12 , cancer research , medicine , leukemia , chemistry , cytotoxic t cell , biology , in vitro , immune system , biochemistry
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.