{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,5]],"date-time":"2026-01-05T17:15:35Z","timestamp":1767633335511,"version":"3.48.0"},"reference-count":44,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2026,1,3]],"date-time":"2026-01-03T00:00:00Z","timestamp":1767398400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Nuclear (Shanghai) Pharmaceutical Technology Co., Ltd."},{"name":"the Science and Technology Commission of Shanghai Municipality, China","award":["19411951100"],"award-info":[{"award-number":["19411951100"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>MICB-targeting CAR-NK (chimeric antigen receptor-modified natural killer cells) therapy may serve as off-the-shelf immunotherapy. We designed soluble Anti-MICB-scFv blocks tumor immune evasion targeting the MICB antigen, thereby enhancing CAR-NK cytotoxicity while reactivating endogenous immune attacks against malignancies. The Anti-MICB-CAR includes two Anti-MICB-scFv connected by an F2A linker, the CD8 hinge and transmembrane domain, the 4-1BB co-stimulatory domain, the CD3\u03b6 activation domain, and IL-15. The expression efficiency of Anti-MICB-CAR in NK cells was investigated by flow cytometry; ELISA demonstrated that Anti-MICB-CAR-NK secreted free Anti-MICB-scFv and detected IL-15 secretion. Flow cytometry and CCK8 were utilized to study Anti-MICB-CAR-NK on tumor cell viability. The PANC-1 xenograft model was established in order to elucidate the anti-tumor effects of Anti-MICB-CAR-NK in vivo. In vitro investigations have demonstrated that the treatment of tumor cells with Anti-MICB-CAR-NK supernatant + NK cells or Anti-MICB-CAR-NK cells not only significantly increased the cytotoxic activity of tumor cells, but also secreted and produced higher levels of IL-15, IFN-\u03b3, TNF-\u03b1, perforin, and granzyme B compared with NK cells. Anti-MICB-CAR-NK cells exhibit strong cytotoxic activity against tumor cells with high MICB expression. In vivo, Anti-MICB-CAR-NK cells exhibited a substantial inhibitory effect on tumor growth. The IHC results reveal that Anti-MICB-CAR-NK cells show a more pronounced ability to infiltrate the tumor. We demonstrated the successful expression of Anti-MICB-CAR in NK cells, which enhances the anti-tumor activity of NK cells both in vitro and in vivo. This stress ligand-targeting approach provides a promising strategy for solid tumors.<\/jats:p>","DOI":"10.3390\/ijms27010500","type":"journal-article","created":{"date-parts":[[2026,1,5]],"date-time":"2026-01-05T12:38:56Z","timestamp":1767616736000},"page":"500","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["A Novel MICB-Targeting CAR-NK Cells for the Treatment of Pancreatic Cancer"],"prefix":"10.3390","volume":"27","author":[{"given":"Weiyang","family":"Jin","sequence":"first","affiliation":[{"name":"International Research Center for Biological Sciences, Ministry of Science and Technology, Shanghai Ocean University, Shanghai 201306, China"},{"name":"Aquatic Animal Genetics and Breeding Center, Shanghai Ocean University, Shanghai 201306, China"},{"name":"National Aquatic Animal Pathogen Collection Center, Shanghai Ocean University, Shanghai 201306, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mengying","family":"Wang","sequence":"additional","affiliation":[{"name":"International Research Center for Biological Sciences, Ministry of Science and Technology, Shanghai Ocean University, Shanghai 201306, China"},{"name":"Aquatic Animal Genetics and Breeding Center, Shanghai Ocean University, Shanghai 201306, China"},{"name":"National Aquatic Animal Pathogen Collection Center, Shanghai Ocean University, Shanghai 201306, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jingwei","family":"Wang","sequence":"additional","affiliation":[{"name":"Medical Research Center, Academy of Chinese Medical Sciences, Zhejiang Chinese Medical University, Hangzhou 310050, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jinyi","family":"Fan","sequence":"additional","affiliation":[{"name":"International Research Center for Biological Sciences, Ministry of Science and Technology, Shanghai Ocean University, Shanghai 201306, China"},{"name":"Aquatic Animal Genetics and Breeding Center, Shanghai Ocean University, Shanghai 201306, China"},{"name":"National Aquatic Animal Pathogen Collection Center, Shanghai Ocean University, Shanghai 201306, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jie","family":"Fang","sequence":"additional","affiliation":[{"name":"Zhejiang Provincial Laboratory of Experimental Animal\u2019s & Nonclinical Laboratory Studies, Hangzhou Medical College, Hangzhou 310013, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Guanghua","family":"Yang","sequence":"additional","affiliation":[{"name":"International Research Center for Biological Sciences, Ministry of Science and Technology, Shanghai Ocean University, Shanghai 201306, China"},{"name":"Aquatic Animal Genetics and Breeding Center, Shanghai Ocean University, Shanghai 201306, China"},{"name":"National Aquatic Animal Pathogen Collection Center, Shanghai Ocean University, Shanghai 201306, China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2026,1,3]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"3673","DOI":"10.1182\/blood.2022016676","article-title":"CAR T-cell therapy: Which product for which patient?","volume":"139","author":"Strati","year":"2022","journal-title":"Blood"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"342","DOI":"10.1038\/s41571-022-00607-3","article-title":"Preparing for CAR T cell therapy: Patient selection, bridging therapies and lymphodepletion","volume":"19","author":"Amini","year":"2022","journal-title":"Nat. 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