Evaluation of Nonviral piggyBac and lentiviral Vector in Functions of CD19chimeric Antigen Receptor T Cells and Their Antitumor Activity for CD19+ Tumor Cells
| Autor: | 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, Yan Sun, Qijun Qian |
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| Rok vydání: | 2022 |
| Předmět: |
Cytotoxicity
Immunologic T-Lymphocytes Antigens CD19 Genetic Vectors Immunology T cells Mice SCID Immunotherapy Adoptive Mice Inbred NOD Cell Line Tumor Neoplasms B lymphoma Animals Humans Immunology and Allergy Cells Cultured Original Research Mice Knockout lentiviral Receptors Chimeric Antigen chimeric antigen receptor CD19 piggyBac Lentivirus RC581-607 Xenograft Model Antitumor Assays Tumor Burden DNA Transposable Elements Female Immunologic diseases. Allergy |
| Zdroj: | Frontiers in Immunology Frontiers in Immunology, Vol 12 (2022) |
| ISSN: | 1664-3224 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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