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We found that these targeted NK cells were specifically activated upon recognition of all evaluated HER-2 positive tumor cells, including autologous targets, as indicated by high levels of cytokine secretion as well as degranulation. The magnitude of this specific response correlated with the level of HER-2 expression on the tumor cells. Finally, these receptor transduced NK cells, but not their mock transduced counterpart, efficiently eradicated tumor cells in<jats:italic>RAG2<\/jats:italic>knockout mice as visualized by in vivo imaging. Taken together, these results indicate that the expression of this activating receptor overrides inhibitory signals in primary human NK cells and directs them specifically toward HER-2 expressing tumor cells both in vitro and in vivo.<\/jats:p>","DOI":"10.1073\/pnas.0804788105","type":"journal-article","created":{"date-parts":[[2008,11,6]],"date-time":"2008-11-06T02:25:33Z","timestamp":1225938333000},"page":"17481-17486","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":172,"title":["Engineering antigen-specific primary human NK cells against HER-2 positive carcinomas"],"prefix":"10.1073","volume":"105","author":[{"given":"Anna","family":"Kruschinski","sequence":"first","affiliation":[{"name":"Max-Delbr\u00fcck Center for Molecular Medicine, D-13092 Berlin, Germany;"}]},{"given":"Andreas","family":"Moosmann","sequence":"additional","affiliation":[{"name":"Clinical Cooperation Group Molecular Oncology, University of Munich, Marchioninistrasse 25, 81377 Munich, Germany;"}]},{"given":"Isabel","family":"Poschke","sequence":"additional","affiliation":[{"name":"Cancer Centrum Karolinska, Karolinska Institutet, 171 76 Stockholm, Sweden;"}]},{"given":"H\u00e5kan","family":"Norell","sequence":"additional","affiliation":[{"name":"Cancer Centrum Karolinska, Karolinska Institutet, 171 76 Stockholm, Sweden;"},{"name":"Department of Surgery, Hollings Cancer Center, Medical University of South Carolina, Charleston, SC 29425;"}]},{"given":"Markus","family":"Chmielewski","sequence":"additional","affiliation":[{"name":"Department I of Internal Medicine, Tumor Genetics, and Center for Molecular Medicine Cologne, University of Cologne, D-50931 Cologne, Germany;"}]},{"given":"Barbara","family":"Seliger","sequence":"additional","affiliation":[{"name":"Martin Luther University Halle, Wittenberg, Institute of Medical Immunology, 06112 Halle, Germany; and"}]},{"given":"Rolf","family":"Kiessling","sequence":"additional","affiliation":[{"name":"Cancer Centrum Karolinska, Karolinska Institutet, 171 76 Stockholm, Sweden;"}]},{"given":"Thomas","family":"Blankenstein","sequence":"additional","affiliation":[{"name":"Max-Delbr\u00fcck Center for Molecular Medicine, D-13092 Berlin, Germany;"},{"name":"Institute of Immunology, Charite Campus Benjamin Franklin, D-12203 Berlin, Germany"}]},{"given":"Hinrich","family":"Abken","sequence":"additional","affiliation":[{"name":"Department I of Internal Medicine, Tumor Genetics, and Center for Molecular Medicine Cologne, University of Cologne, D-50931 Cologne, Germany;"}]},{"given":"Jehad","family":"Charo","sequence":"additional","affiliation":[{"name":"Max-Delbr\u00fcck Center for Molecular Medicine, D-13092 Berlin, Germany;"}]}],"member":"341","published-online":{"date-parts":[[2008,11,11]]},"reference":[{"key":"e_1_3_3_1_2","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-04-2006"},{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrc2355"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1038\/ni1102-999"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1093\/jnci\/88.2.100"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1002\/eji.200425041"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0065-2776(08)60664-1"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.immunol.23.021704.115526"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-065X.2006.00458.x"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1038\/319675a0"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0952-7915(97)80051-9"},{"key":"e_1_3_3_11_2","doi-asserted-by":"crossref","first-page":"4207","DOI":"10.4049\/jimmunol.163.8.4207","article-title":"NK cell triggering by the human costimulatory molecules CD80 and CD86","volume":"163","author":"Wilson JL","year":"1999","unstructured":"JL Wilson, et al., NK cell triggering by the human costimulatory molecules CD80 and CD86. 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