{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T18:28:53Z","timestamp":1790706533228,"version":"4.1.0"},"reference-count":48,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2022,12,8]],"date-time":"2022-12-08T00:00:00Z","timestamp":1670457600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Hematological Oncology"],"published-print":{"date-parts":[[2023,8]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Natural killer (NK) cells are components of the innate immune system which play a pivotal role in cancer cell surveillance. Despite promising results in clinical trials, the use of NK\u2010based therapies is limited due to unsatisfactory efficiencies and safety issues. In recent years, exosomes have emerged as a powerful, natural therapeutic tool. Since exosomes are known to carry cargos that reflect the cellular makeup of their cell of origin, we were prompted to test whether NK\u2010derived exosomes (NK\n                    <jats:italic>exo<\/jats:italic>\n                    ) maintain the anti\u2010leukemia capacity of NK\u2010cells. We found NK92MI\u2010cells to secrete large amounts of 100\u2013200\u00a0nm cap\u2010shaped particles expressing exosomal and NK biomarkers (CD63, CD81, CD56). We demonstrated that NK\n                    <jats:italic>exo<\/jats:italic>\n                    exert a potent, selective, anti\u2010leukemia effect on all leukemia cell\u2010lines tested. Furthermore, NK\n                    <jats:italic>exo<\/jats:italic>\n                    eliminated leukemia cells isolated from patients with acute and chronic leukemia and inhibited hematopoietic colony growth. While leukemia cells were targeted and severely affected by NK\n                    <jats:italic>exo<\/jats:italic>\n                    , healthy B\u2010cells remained unaffected, indicating a selective effect. This selectivity was further confirmed by demonstrating that NK\n                    <jats:italic>exo<\/jats:italic>\n                    were specifically taken up by leukemic cells but not by healthy B\u2010cells. Our in vivo data support our in vitro and ex vivo findings and demonstrate improved human\u2010CD45\n                    <jats:sup>+<\/jats:sup>\n                    leukemia blast counts and overall survival in NK\n                    <jats:italic>exo<\/jats:italic>\n                    treated humanized acute myeloid leukemia (HL\u201060) xenograft mice thus supporting the assumption that NK\n                    <jats:italic>exo<\/jats:italic>\n                    possess an anti\u2010leukemia effect. Pending further analyses, our findings provide the pre\u2010clinical evidence needed to test the NKe\n                    <jats:italic>xo<\/jats:italic>\n                    approach in future pre\u2010clinical and clinical studies to ultimately develop an acellular \u201coff\u2010the\u2010shelf\u201d product to treat leukemia.\n                  <\/jats:p>","DOI":"10.1002\/hon.3111","type":"journal-article","created":{"date-parts":[[2022,11,30]],"date-time":"2022-11-30T23:47:48Z","timestamp":1669852068000},"page":"487-498","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":18,"title":["Using natural killer cell\u2010derived exosomes as a cell\u2010free therapy for leukemia"],"prefix":"10.1002","volume":"41","author":[{"given":"Aladin","family":"Samara","sequence":"first","affiliation":[{"name":"Felsenstein Medical Research Center Rabin Medical Center  Petah Tikva Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Anbar","sequence":"additional","affiliation":[{"name":"Felsenstein Medical Research Center Rabin Medical Center  Petah Tikva Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Saar","family":"Shapira","sequence":"additional","affiliation":[{"name":"Felsenstein Medical Research Center Rabin Medical Center  Petah Tikva Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna","family":"Zemlyansky","sequence":"additional","affiliation":[{"name":"The Rina Zaizov Pediatric Hematology and Oncology Division Schneider Children's Medical Center Rabin Medical Center  Petah Tikva Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alla","family":"Zozovsky","sequence":"additional","affiliation":[{"name":"The Rina Zaizov Pediatric Hematology and Oncology Division Schneider Children's Medical Center Rabin Medical Center  Petah Tikva 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Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2022,12,8]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2017.01.016"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.aar6711"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrclinonc.2018.19"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbmt.2018.12.758"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1093\/jnci\/djz017"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41573\u2010019\u20100052\u20101"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41577\u2010018\u20100061\u2010z"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1038\/ni.3518"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41571\u2010020\u20100426\u20107"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41590\u2010020\u20100728\u2010z"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1056\/nejmoa1910607"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1158\/1535\u20107163.MCT\u201012\u20100692"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598\u2010017\u201014661\u2010w"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1097\/PPO.0000000000000156"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.1111\/bjh.16310"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2016.00091"},{"key":"e_1_2_8_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbalip.2013.10.004"},{"key":"e_1_2_8_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biocel.2012.08.007"},{"key":"e_1_2_8_20_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12885\u2010017\u20103958\u20101"},{"key":"e_1_2_8_21_1","doi-asserted-by":"publisher","DOI":"10.1038\/nri2567"},{"key":"e_1_2_8_22_1","doi-asserted-by":"publisher","DOI":"10.3402\/jev.v4.26316"},{"key":"e_1_2_8_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.nano.2015.10.012"},{"key":"e_1_2_8_24_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41392\u2010020\u201000261\u20100"},{"key":"e_1_2_8_25_1","doi-asserted-by":"publisher","DOI":"10.3390\/jcm8101702"},{"key":"e_1_2_8_26_1","doi-asserted-by":"publisher","DOI":"10.1038\/nbt.1807"},{"key":"e_1_2_8_27_1","doi-asserted-by":"publisher","DOI":"10.1080\/25785826.2020.1818482"},{"key":"e_1_2_8_28_1","doi-asserted-by":"publisher","DOI":"10.1097\/CJI.0000000000000179"},{"key":"e_1_2_8_29_1","doi-asserted-by":"publisher","DOI":"10.1002\/0471143030.cb0322s30"},{"key":"e_1_2_8_30_1","doi-asserted-by":"publisher","DOI":"10.1038\/bcj.2015.19"},{"key":"e_1_2_8_31_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1101988"},{"key":"e_1_2_8_32_1","doi-asserted-by":"publisher","DOI":"10.1080\/20013078.2017.1294368"},{"key":"e_1_2_8_33_1","doi-asserted-by":"publisher","DOI":"10.7150\/thno.18752"},{"key":"e_1_2_8_34_1","doi-asserted-by":"publisher","DOI":"10.1158\/0008\u20105472.CAN\u201018\u20100779"},{"key":"e_1_2_8_35_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41417\u2010021\u201000352\u20102"},{"key":"e_1_2_8_36_1","doi-asserted-by":"publisher","DOI":"10.3389\/fcell.2021.698639"},{"key":"e_1_2_8_37_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.imlet.2006.10.001"},{"key":"e_1_2_8_38_1","doi-asserted-by":"publisher","DOI":"10.1080\/20013078.2019.1588538"},{"key":"e_1_2_8_39_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2021.658698"},{"key":"e_1_2_8_40_1","doi-asserted-by":"publisher","DOI":"10.1021\/acsnano.9b10033"},{"key":"e_1_2_8_41_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biomaterials.2018.10.034"},{"key":"e_1_2_8_42_1","doi-asserted-by":"publisher","DOI":"10.3390\/cancers11101560"},{"key":"e_1_2_8_43_1","doi-asserted-by":"publisher","DOI":"10.1007\/978\u20101\u20104939\u20107253\u20101_3"},{"key":"e_1_2_8_44_1","doi-asserted-by":"publisher","DOI":"10.3402\/jev.v2i0.19861"},{"key":"e_1_2_8_45_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajprenal.00434.2006"},{"key":"e_1_2_8_46_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms21134774"},{"key":"e_1_2_8_47_1","doi-asserted-by":"publisher","DOI":"10.1080\/20013078.2018.1442088\/SUPPL_FILE\/ZJEV_A_1442088_SM6568.ZIP"},{"key":"e_1_2_8_48_1","doi-asserted-by":"publisher","DOI":"10.3390\/cells7120273"},{"key":"e_1_2_8_49_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598\u2010017\u201010646\u2010x"}],"container-title":["Hematological 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