{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T15:58:30Z","timestamp":1792166310193,"version":"4.4.0"},"reference-count":52,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2024,6,3]],"date-time":"2024-06-03T00:00:00Z","timestamp":1717372800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81925002"],"award-info":[{"award-number":["81925002"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100012166","name":"National Key Research and Development Program of China","doi-asserted-by":"publisher","award":["2020YFA0112404"],"award-info":[{"award-number":["2020YFA0112404"]}],"id":[{"id":"10.13039\/501100012166","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Cell Proliferation"],"published-print":{"date-parts":[[2024,11]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Chimeric antigen receptor\u2010natural killer (CAR\u2010NK) cell therapy is emerging as a promising cancer treatment, with notable safety and source diversity benefits over CAR\u2010T cells. This study focused on optimizing CAR constructs for NK cells to maximize their therapeutic potential. We designed seven CD19 CAR constructs and expressed them in NK cells using a retroviral system, assessing their tumour\u2010killing efficacy and persistence. Results showed all constructs enhanced tumour\u2010killing and prolonged survival in tumour\u2010bearing mice. In particular, CAR1 (CD8 TMD\u2010CD3\u03b6 SD)\u2010NK cells showed superior efficacy in treating tumour\u2010bearing animals and exhibited enhanced persistence when combined with OX40 co\u2010stimulatory domain. Of note, CAR1\u2010NK cells were most effective at lower effector\u2010to\u2010target ratios, while CAR4 (CD8 TMD\u2010OX40 CD\u2010 Fc\u03b5RI\u03b3 SD) compromised NK cell expansion ability. Superior survival rates were noted in mice treated with CAR1\u2010, CAR2 (CD8 TMD\u2010 Fc\u03b5RI\u03b3 SD)\u2010, CAR3 (CD8 TMD\u2010OX40 CD\u2010 CD3\u03b6 SD)\u2010 and CAR4\u2010NK cells over those treated with CAR5 (CD28 TMD\u2010 Fc\u03b5RI\u03b3 SD)\u2010, CAR6 (CD8 TMD\u20104\u20101BB CD\u2010CD3\u03b6 1\u2010ITAM SD)\u2010 and CAR7 (CD8 TMD\u2010OX40 CD\u2010CD3\u03b6 1\u2010ITAM SD)\u2010NK cells, with CAR5\u2010NK cells showing the weakest anti\u2010tumour activity. Increased expression of exhaustion markers, especially in CAR7\u2010NK cells, suggests that combining CAR\u2010NK cells with immune checkpoint inhibitors might improve anti\u2010tumour outcomes. These findings provide crucial insights for developing CAR\u2010NK cell products for clinical applications.<\/jats:p>","DOI":"10.1111\/cpr.13683","type":"journal-article","created":{"date-parts":[[2024,6,3]],"date-time":"2024-06-03T21:50:10Z","timestamp":1717451410000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":26,"title":["Comparison of seven\n                    <scp>CD19 CAR<\/scp>\n                    designs in engineering\n                    <scp>NK<\/scp>\n                    cells for enhancing anti\u2010tumour activity"],"prefix":"10.1111","volume":"57","author":[{"given":"Yao","family":"Wang","sequence":"first","affiliation":[{"name":"Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences  Guangzhou China"},{"name":"State Key Laboratory of Stem Cell and Reproductive Biology Institute for Stem Cell and Regeneration, Institute of Zoology, Chinese Academy of Sciences  Beijing China"},{"name":"Beijing Institute for Stem Cell and Regenerative Medicine  Beijing China"},{"name":"University of Chinese Academy of Sciences  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jianhuan","family":"Li","sequence":"additional","affiliation":[{"name":"Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences  Guangzhou China"},{"name":"State Key Laboratory of Stem Cell and Reproductive Biology Institute for Stem Cell and Regeneration, Institute of Zoology, Chinese Academy of Sciences  Beijing China"},{"name":"Beijing Institute for Stem Cell and Regenerative Medicine  Beijing China"},{"name":"University of Chinese Academy of Sciences  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhiqian","family":"Wang","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Stem Cell and Reproductive Biology Institute for Stem Cell and Regeneration, Institute of Zoology, Chinese Academy of Sciences  Beijing China"},{"name":"Beijing Institute for Stem Cell and Regenerative Medicine  Beijing China"},{"name":"University of Chinese Academy of Sciences  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanhong","family":"Liu","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Stem Cell and Reproductive Biology Institute for Stem Cell and Regeneration, Institute of Zoology, Chinese Academy of Sciences  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tongjie","family":"Wang","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Stem Cell and Reproductive Biology Institute for Stem Cell and Regeneration, Institute of Zoology, Chinese Academy of Sciences  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mengyun","family":"Zhang","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Stem Cell and Reproductive Biology Institute for Stem Cell and Regeneration, Institute of Zoology, Chinese Academy of Sciences  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chengxiang","family":"Xia","sequence":"additional","affiliation":[{"name":"Beijing Institute for Stem Cell and Regenerative Medicine  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fan","family":"Zhang","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Stem Cell and Reproductive Biology Institute for Stem Cell and Regeneration, Institute of Zoology, Chinese Academy of Sciences  Beijing China"},{"name":"Beijing Institute for Stem Cell and Regenerative Medicine  Beijing China"},{"name":"University of Chinese Academy of Sciences  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dehao","family":"Huang","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Stem Cell and Reproductive Biology Institute for Stem Cell and Regeneration, Institute of Zoology, Chinese Academy of Sciences  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leqiang","family":"Zhang","sequence":"additional","affiliation":[{"name":"Beijing Institute for Stem Cell and Regenerative Medicine  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yaoqin","family":"Zhao","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Stem Cell and Reproductive Biology Institute for Stem Cell and Regeneration, Institute of Zoology, Chinese Academy of Sciences  Beijing China"},{"name":"Beijing Institute for Stem Cell and Regenerative Medicine  Beijing China"},{"name":"GMU\u2010GIBH Joint School of Life Sciences Guangzhou Medical University  Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lijuan","family":"Liu","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Stem Cell and Reproductive Biology Institute for Stem Cell and Regeneration, Institute of Zoology, Chinese Academy of Sciences  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanping","family":"Zhu","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Stem Cell and Reproductive Biology Institute for Stem Cell and Regeneration, Institute of Zoology, Chinese Academy of Sciences  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hanmeng","family":"Qi","sequence":"additional","affiliation":[{"name":"Beijing Institute for Stem Cell and Regenerative Medicine  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaofan","family":"Zhu","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Experimental Hematology &amp; National Clinical Research Center for Blood Diseases Institute of Hematology &amp; Blood Diseases Hospital, Chinese Academy of Medical Sciences &amp; Peking Union Medical College  Tianjin China"},{"name":"Center for Stem Cell Medicine &amp; Department of Stem Cell and Regenerative Medicine Chinese Academy of Medical Sciences &amp; Peking Union Medical College  Tianjin China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenbin","family":"Qian","sequence":"additional","affiliation":[{"name":"Department of Hematology, the Second Affiliated Hospital, College of Medicine Zhejiang University  Zhejiang Hangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fangxiao","family":"Hu","sequence":"additional","affiliation":[{"name":"Beijing Institute for Stem Cell and Regenerative Medicine  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jinyong","family":"Wang","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Stem Cell and Reproductive Biology Institute for Stem Cell and Regeneration, Institute of Zoology, Chinese Academy of Sciences  Beijing China"},{"name":"Beijing Institute for Stem Cell and Regenerative Medicine  Beijing China"},{"name":"University of Chinese Academy of Sciences  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2024,6,3]]},"reference":[{"key":"e_1_2_8_2_1","first-page":"127","article-title":"Generation of effector T cells expressing chimeric T cell receptor with antibody type\u2010specificity","volume":"21","author":"Gross G","year":"1989","journal-title":"Transplant Proc"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.155.2.1000"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41587-020-0462-y"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1186\/s40425-018-0460-5"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41571-019-0297-y"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13045-017-0553-5"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1158\/2159-8290.CD-19-0945"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(91)90327-U"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1089\/hum.2017.241"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.leu.2403302"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13045-022-01244-0"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2022.878209"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1126\/scisignal.aan1088"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41591-018-0290-5"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ebiom.2020.102931"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrd4597"},{"key":"e_1_2_8_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ccell.2015.09.004"},{"key":"e_1_2_8_19_1","doi-asserted-by":"publisher","DOI":"10.1158\/1535-7163.MCT-17-1097"},{"key":"e_1_2_8_20_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12967-023-04292-3"},{"key":"e_1_2_8_21_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2020.01046"},{"key":"e_1_2_8_22_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41577-022-00732-1"},{"key":"e_1_2_8_23_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1910607"},{"key":"e_1_2_8_24_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13046-022-02327-z"},{"key":"e_1_2_8_25_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2004-12-4797"},{"key":"e_1_2_8_26_1","doi-asserted-by":"publisher","DOI":"10.1158\/2326-6074.TUMIMM19-B64"},{"key":"e_1_2_8_27_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41590-023-01659-y"},{"key":"e_1_2_8_28_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13045-023-01455-z"},{"key":"e_1_2_8_29_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.290.5489.84"},{"key":"e_1_2_8_30_1","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.54854"},{"key":"e_1_2_8_31_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jcyt.2020.06.003"},{"key":"e_1_2_8_32_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.92.15.6733"},{"key":"e_1_2_8_33_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V96.4.1206.h8001206_1206_1214"},{"key":"e_1_2_8_34_1","doi-asserted-by":"publisher","DOI":"10.1038\/leu.2017.226"},{"key":"e_1_2_8_35_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0161-5890(97)00144-2"},{"key":"e_1_2_8_36_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.146.5.1571"},{"key":"e_1_2_8_37_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jim.2004.08.008"},{"key":"e_1_2_8_38_1","doi-asserted-by":"publisher","DOI":"10.1189\/jlb.0611308"},{"key":"e_1_2_8_39_1","doi-asserted-by":"publisher","DOI":"10.1002\/eji.202049028"},{"key":"e_1_2_8_40_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.stem.2021.08.013"},{"key":"e_1_2_8_41_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2023.1303605"},{"key":"e_1_2_8_42_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.175.7.4611"},{"key":"e_1_2_8_43_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.coi.2009.02.009"},{"key":"e_1_2_8_44_1","doi-asserted-by":"publisher","DOI":"10.1038\/ni1581"},{"key":"e_1_2_8_45_1","doi-asserted-by":"publisher","DOI":"10.1002\/ijc.25960"},{"key":"e_1_2_8_46_1","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.aba7308"},{"key":"e_1_2_8_47_1","doi-asserted-by":"publisher","DOI":"10.3390\/cancers13010038"},{"key":"e_1_2_8_48_1","doi-asserted-by":"publisher","DOI":"10.3390\/cells9051182"},{"key":"e_1_2_8_49_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2020.07.011"},{"key":"e_1_2_8_50_1","doi-asserted-by":"publisher","DOI":"10.1158\/2326-6066.CIR-15-0048"},{"key":"e_1_2_8_51_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymthe.2017.06.008"},{"key":"e_1_2_8_52_1","doi-asserted-by":"publisher","DOI":"10.1111\/imm.13464"},{"key":"e_1_2_8_53_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2022.1081546"}],"updated-by":[{"DOI":"10.1111\/cpr.70098","type":"correction","label":"Correction","source":"publisher","updated":{"date-parts":[[2025,7,21]],"date-time":"2025-07-21T00:00:00Z","timestamp":1753056000000}}],"container-title":["Cell Proliferation"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/cpr.13683","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,11,4]],"date-time":"2024-11-04T06:53:35Z","timestamp":1730703215000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/cpr.13683"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,6,3]]},"references-count":52,"journal-issue":{"issue":"11","published-print":{"date-parts":[[2024,11]]}},"alternative-id":["10.1111\/cpr.13683"],"URL":"https:\/\/doi.org\/10.1111\/cpr.13683","archive":["Portico"],"relation":{},"ISSN":["0960-7722","1365-2184"],"issn-type":[{"value":"0960-7722","type":"print"},{"value":"1365-2184","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,6,3]]},"assertion":[{"value":"2024-04-18","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-05-20","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-06-03","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e13683"}}