2026-10-13T18:32:21Z https://api.figshare.com/v2/oai

oai:figshare.com:article/34039452 2026-10-01T05:39:29Z category_696 portal_316 item_type_3 month_year_10_2026

Data Sheet 1_eVLP-mediated CREM editing enhances cytotoxicity of bicistronic IL-15-armored CD19/BCMA dual-target CAR-NK cells.pdf Fengqin Shang (11334561) Guanlie Li (10678716) Shiting Gong (25152819) Lijiao Zhao (709126) Bingyu Niu (17385496) Hanyi Chen (4855570) Yuchen Fu (534671) Lijun Zhao (418243) Jianxun Wang (290485) Yuanyuan Shi (563992) Genetic Immunology cancer immunotherapy CAR-NK cells CAR-T cells CD19/BCMA dual targeting CREM editing engineered virus-like particles genome editing IL-15 armoring <p>Chimeric antigen receptor (CAR)-engineered natural killer (NK) cells represent a promising platform for cancer immunotherapy; however, optimization of CAR architecture and additional engineering strategies remain necessary to improve their functional activity. In this study, we generated CD19/BCMA dual-target CAR constructs based on tandem and bicistronic configurations with or without membrane-bound interleukin-15 (mbIL-15), and further evaluated engineered virus-like particle (eVLP)-mediated CREM editing as an additional strategy for CAR-NK cell engineering. Four CAR configurations were evaluated in primary human T and NK cells for CAR expression, cytotoxicity, cytokine production, and proliferative activity. Bicistronic CD19/BCMA CAR-mbIL-15 cells exhibited enhanced functional activity compared with corresponding tandem CAR-mbIL-15 cells, including increased tumor-cell killing and activation-associated functional responses in vitro. In a CD19/BCMA-positive leukemia xenograft model, bicistronic CD19/BCMA CAR-mbIL-15 T and NK cells reduced tumor burden, delayed disease progression, and prolonged survival. Furthermore, eVLP-mediated CREM editing achieved efficient genome modification in primary NK cells and remained compatible with subsequent CAR engineering. CREM-edited CAR-NK cells exhibited increased cytotoxic activity compared with unedited CAR-NK cells in vitro. Collectively, these findings support the development of modular CAR-NK engineering strategies integrating CAR architecture optimization, membrane-bound cytokine armoring, and transient genome engineering.</p> 2026-10-01T05:39:29Z Dataset Dataset 10.3389/fimmu.2026.1976202.s001 https://figshare.com/articles/dataset/Data_Sheet_1_eVLP-mediated_CREM_editing_enhances_cytotoxicity_of_bicistronic_IL-15-armored_CD19_BCMA_dual-target_CAR-NK_cells_pdf/34039452 CC BY 4.0