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

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

JOURNAL=Frontiers in Immunology

VOLUME=Volume 12 - 2021

YEAR=2022

URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2021.802705

DOI=10.3389/fimmu.2021.802705

ISSN=1664-3224

ABSTRACT=Non-viral transposon piggyBac (PB) and lentiviral (LV) vector have been used to deliver chimeric antigen receptor (CAR) into T cells. To understand the differences of PB with LV in functions of CAR T cells, we constructed CAR to targeting CD19 with PB or LV vectors, delivered pbCAR or lvCAR into T cells and generated CD19pbCAR T or CD19lvCAR T cells. The results showed that both of CD19CAR T cells had strong cytotoxicity and increase of IFN-γ levels when incubating with Raji cells. TNF-α increased in CD19pbCAR T cells, while IL-10 increased in CD19lvCAR T cells. CD19pbCAR T cells showed the similar strong anti-tumor activity as CD19lvCAR T cells in Raji cell-induced mouse models and had slight decreased effect on mouse weight but increased the murine survival. Subsequently, the CD19pbCAR T cells demonstrated significant inhibition of Raji cell-induced tumor in vivo with the high concentration but not the low and middle one. The CD19pbCAR T cells in vivo distributed mostly in mesenteric lymphonodes, bone marrow of femur, spleen, kidney and lung, exhibiting specific accumulation at CD19-rich site or tumor location and increased CAR copy number at day 7. These results demonstrate that pbCAR has its own properties in activities and functions of pbCAR T cells, which makes it a valuable tool for CAR T immunotherapy.