{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,1]],"date-time":"2026-06-01T06:02:23Z","timestamp":1780293743819,"version":"3.54.0"},"reference-count":33,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,6,1]],"date-time":"2026-06-01T00:00:00Z","timestamp":1780272000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003725","name":"National Research Foundation of Korea","doi-asserted-by":"publisher","award":["RS-2025-00557411,  RS-2019-NR40073, RS-2026-25469366, RS-2023-00218543"],"award-info":[{"award-number":["RS-2025-00557411,  RS-2019-NR40073, RS-2026-25469366, RS-2023-00218543"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>Chimeric antigen receptor-engineered natural killer (CAR-NK) cells have emerged as a promising strategy for cancer immunotherapy; however, their efficacy against solid tumors remains limited by inefficient tumor trafficking and impaired cytotoxic function within the tumor microenvironment. Here, we investigated whether a non-genetic chemical priming strategy could pre-arm CAR-NK cells and enhance their migratory and cytotoxic functions.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Based on our previous findings that transient exposure to 25 kDa branched polyethylenimine (25KbPEI) induces a primed phenotype, mesothelin-targeting CAR-NK-92 cells were chemically primed and evaluated for migration, cytotoxicity, killing dynamics, perforin accumulation, cytokine production, and in vivo antitumor efficacy in a SKOV3 xenograft model.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Chemical priming significantly enhanced cytotoxicity and degranulation against ovarian cancer cells without compromising cell viability. Primed CAR-NK cells showed increased CCR7 expression and improved tumor-directed migration. Live-cell imaging further revealed accelerated target engagement and shortened killing time, indicating enhanced cytotoxic kinetics. In addition, chemical priming increased perforin accumulation and IFN-\u03b3 production. In the SKOV3 xenograft model, primed CAR-NK cells achieved superior tumor control and increased intratumoral infiltration compared with non-primed CAR-NK cells, while maintaining a favorable safety profile.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Discussion<\/jats:title>\n                    <jats:p>Collectively, these findings demonstrate that chemical priming enhances CAR-NK cell function and provides a promising non-genetic strategy to improve CAR-NK cell activity against solid tumor models.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fimmu.2026.1860442","type":"journal-article","created":{"date-parts":[[2026,6,1]],"date-time":"2026-06-01T05:24:31Z","timestamp":1780291471000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Chemical priming potentiates mesothelin-targeting chimeric antigen receptor-engineered NK-92 antitumor activity by improving tumor trafficking and cytotoxic killing dynamics"],"prefix":"10.3389","volume":"17","author":[{"given":"Ki Seo","family":"Ryu","sequence":"first","affiliation":[{"name":"Department of Biomedical Science, Division of Life Science, CHA University","place":["Seongnam-si, Republic of Korea"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hail","family":"Park","sequence":"additional","affiliation":[{"name":"Department of Biomedical Science, Division of Life Science, CHA University","place":["Seongnam-si, Republic of Korea"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eunchong","family":"Maeng","sequence":"additional","affiliation":[{"name":"Department of Biomedical Science, Division of Life Science, CHA University","place":["Seongnam-si, Republic of Korea"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jun-Yeon","family":"Lim","sequence":"additional","affiliation":[{"name":"Department of Biomedical Science, Division of Life Science, CHA University","place":["Seongnam-si, Republic of Korea"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Duck","family":"Cho","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine and Genetics, Samsung Medical Center, School of Medicine, Sungkyunkwan University","place":["Seoul, Republic of Korea"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Seung Hee","family":"Choi","sequence":"additional","affiliation":[{"name":"Department of Biomedical Science, Division of Life Science, CHA University","place":["Seongnam-si, Republic of Korea"]},{"name":"Northwestern Medicine Malnati Brain Tumor Institute of the Lurie Comprehensive Cancer Center, Feinberg School of Medicine, Northwestern University","place":["Chicago, IL, United States"]},{"name":"Department of Neurological Surgery, Northwestern University, Feinberg School of Medicine","place":["Chicago, IL, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kyung-Soon","family":"Park","sequence":"additional","affiliation":[{"name":"Department of Biomedical Science, Division of Life Science, CHA University","place":["Seongnam-si, Republic of Korea"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,6,1]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1038\/s41577-019-0139-2","article-title":"Immunometabolism and natural killer cell responses","volume":"19","author":"O'Brien","year":"2019","journal-title":"Nat Rev Immunol"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1038\/s41568-022-00491-0","article-title":"Natural killer cells in antitumour adoptive cell immunotherapy","volume":"22","author":"Laskowski","year":"2022","journal-title":"Nat Rev Cancer"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1038\/s41590-024-01883-0","article-title":"High-dimensional single-cell analysis of human natural killer cell heterogeneity","volume":"25","author":"Rebuffet","year":"2024","journal-title":"Nat Immunol"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.immunol.23.021704.115526","article-title":"NK cell recognition","volume":"23","author":"Lanier","year":"2005","journal-title":"Annu Rev Immunol"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1126\/science.1198687","article-title":"Innate or adaptive immunity? 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