{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T06:01:22Z","timestamp":1790834482507,"version":"4.1.0"},"reference-count":25,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T00:00:00Z","timestamp":1790812800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:p>\n                    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\n                    <jats:italic>in vitro<\/jats:italic>\n                    . 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\n                    <jats:italic>in vitro<\/jats:italic>\n                    . Collectively, these findings support the development of modular CAR-NK engineering strategies integrating CAR architecture optimization, membrane-bound cytokine armoring, and transient genome engineering.\n                  <\/jats:p>","DOI":"10.3389\/fimmu.2026.1976202","type":"journal-article","created":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T05:41:37Z","timestamp":1790833297000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["eVLP-mediated CREM editing enhances cytotoxicity of bicistronic IL-15-armored CD19\/BCMA dual-target CAR-NK cells"],"prefix":"10.3389","volume":"17","author":[{"given":"Fengqin","family":"Shang","sequence":"first","affiliation":[{"name":"Shenzhen Cell Valley Biopharmaceuticals Group Co., Ltd.","place":["Shenzhen, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guanlie","family":"Li","sequence":"additional","affiliation":[{"name":"Shenzhen Cell Valley Biopharmaceuticals Group Co., Ltd.","place":["Shenzhen, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shiting","family":"Gong","sequence":"additional","affiliation":[{"name":"Shenzhen Cell Valley Biopharmaceuticals Group Co., Ltd.","place":["Shenzhen, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lijiao","family":"Zhao","sequence":"additional","affiliation":[{"name":"Shenzhen Cell Valley Biopharmaceuticals Group Co., Ltd.","place":["Shenzhen, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bingyu","family":"Niu","sequence":"additional","affiliation":[{"name":"Shenzhen Cell Valley Biopharmaceuticals Group Co., Ltd.","place":["Shenzhen, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hanyi","family":"Chen","sequence":"additional","affiliation":[{"name":"Shenzhen Cell Valley Biopharmaceuticals Group Co., Ltd.","place":["Shenzhen, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuchen","family":"Fu","sequence":"additional","affiliation":[{"name":"Shenzhen Cell Valley Biopharmaceuticals Group Co., Ltd.","place":["Shenzhen, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lijun","family":"Zhao","sequence":"additional","affiliation":[{"name":"Shenzhen Cell Valley Biopharmaceuticals Group Co., Ltd.","place":["Shenzhen, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jianxun","family":"Wang","sequence":"additional","affiliation":[{"name":"Shenzhen Cell Valley Biopharmaceuticals Group Co., Ltd.","place":["Shenzhen, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuanyuan","family":"Shi","sequence":"additional","affiliation":[{"name":"Shenzhen Cell Valley Biopharmaceuticals Group Co., Ltd.","place":["Shenzhen, 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