Frontiers in Immunology (Jan 2022)

Evaluation of Nonviral piggyBac and lentiviral Vector in Functions of CD19chimeric Antigen Receptor T Cells and Their Antitumor Activity for CD19+ Tumor Cells

  • Zhicai Lin,
  • Xiangzhen Liu,
  • Tao Liu,
  • Haixia Gao,
  • Sitong Wang,
  • Xingli Zhu,
  • Lijie Rong,
  • Jingbo Cheng,
  • Zhigang Cai,
  • Fu Xu,
  • Xue Tan,
  • Linjie Lv,
  • Zhong Li,
  • Zhong Li,
  • Yan Sun,
  • Qijun Qian,
  • Qijun Qian,
  • Qijun Qian

DOI
https://doi.org/10.3389/fimmu.2021.802705
Journal volume & issue
Vol. 12

Abstract

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Nonviral transposon piggyBac (PB) and lentiviral (LV) vectors have been used to deliver chimeric antigen receptor (CAR) to T cells. To understand the differences in the effects of PB and LV on CAR T-cell functions, a CAR targeting CD19 was cloned into PB and LV vectors, and the resulting pbCAR and lvCAR were delivered to T cells to generate CD19pbCAR and CD19lvCAR T cells. Both CD19CAR T-cell types were strongly cytotoxic and secreted high IFN-γ levels when incubated with Raji cells. TNF-α increased in CD19pbCAR T cells, whereas IL-10 increased in CD19lvCAR T cells. CD19pbCAR and CD19lvCAR T cells showed similar strong anti-tumor activity in Raji cell-induced mouse models, slightly reducing mouse weight while enhancing mouse survival. High, but not low or moderate, concentrations of CD19pbCAR T cells significantly inhibited Raji cell-induced tumor growth in vivo. These CD19pbCAR T cells were distributed mostly in mesenteric lymph nodes, bone marrow of the femur, spleen, kidneys, and lungs, specifically accumulating at CD19-rich sites and CD19-positive tumors, with CAR copy number being increased on day 7. These results indicate that pbCAR has its specific activities and functions in pbCAR T cells, making it a valuable tool for CAR T-cell immunotherapy.

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