{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,5]],"date-time":"2026-11-05T14:44:39Z","timestamp":1793889879685,"version":"4.8.0"},"reference-count":51,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2012,2,28]],"date-time":"2012-02-28T00:00:00Z","timestamp":1330387200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J Cellular Molecular Medi"],"published-print":{"date-parts":[[2012,3]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Treatment of high\u2010risk neuroblastoma (NB) represents a major challenge in paediatric oncology. Alternative therapeutic strategies include antibodies targeting the disialoganglioside GD<jats:sub>2<\/jats:sub>, which is expressed at high levels on NB cells, and infusion of donor\u2010derived natural killer (NK) cells. To combine specific antibody\u2010mediated recognition of NB cells with the potent cytotoxic activity of NK cells, here we generated clonal derivatives of the clinically applicable human NK cell line NK\u201092 that stably express a GD<jats:sub>2<\/jats:sub>\u2010specific chimeric antigen receptor (CAR) comprising an anti\u2010GD<jats:sub>2<\/jats:sub> ch14.18 single chain Fv antibody fusion protein with CD3\u2010\u03b6 chain as a signalling moiety. CAR expression by gene\u2010modified NK cells facilitated effective recognition and elimination of established GD<jats:sub>2<\/jats:sub> expressing NB cells, which were resistant to parental NK\u201092. In the case of intrinsically NK\u2010sensitive NB cell lines, we observed markedly increased cell killing activity of retargeted NK\u201092 cells. Enhanced cell killing was strictly dependent on specific recognition of the target antigen and could be blocked by GD<jats:sub>2<\/jats:sub>\u2010specific antibody or anti\u2010idiotypic antibody occupying the CAR\u2019s cell recognition domain. Importantly, strongly enhanced cytotoxicity of the GD<jats:sub>2<\/jats:sub>\u2010specific NK cells was also found against primary NB cells and GD<jats:sub>2<\/jats:sub> expressing tumour cells of other origins, demonstrating the potential clinical utility of the retargeted effector cells.<\/jats:p>","DOI":"10.1111\/j.1582-4934.2011.01343.x","type":"journal-article","created":{"date-parts":[[2011,5,20]],"date-time":"2011-05-20T11:42:19Z","timestamp":1305891739000},"page":"569-581","source":"Crossref","is-referenced-by-count":171,"title":["NK cells engineered to express a GD<sub>2<\/sub>\u2010specific antigen receptor display built\u2010in ADCC\u2010like activity against tumour cells of neuroectodermal 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