{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T15:33:57Z","timestamp":1791214437372,"version":"4.1.0"},"reference-count":73,"publisher":"Oxford University Press (OUP)","issue":"7","license":[{"start":{"date-parts":[[2015,4,1]],"date-time":"2015-04-01T00:00:00Z","timestamp":1427846400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2015,4,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>NK cells are emerging as new effectors for immunotherapy of cancer. In particular, the genetic engraftment of chimeric Ag receptors (CARs) in NK cells is a promising strategy to redirect NK cells to otherwise NK cell\u2013resistant tumor cells. On the basis of DNAX-activation protein 12 (DAP12), a signaling adaptor molecule involved in signal transduction of activating NK cell receptors, we generated a new type of CAR targeting the prostate stem cell Ag (PSCA). We demonstrate in this article that this CAR, designated anti\u2013PSCA-DAP12, consisting of DAP12 fused to the anti-PSCA single-chain Ab fragment scFv(AM1) confers improved cytotoxicity to the NK cell line YTS against PSCA-positive tumor cells when compared with a CAR containing the CD3\u03b6 signaling chain. Further analyses revealed phosphorylation of the DAP12-associated ZAP-70 kinase and IFN-\u03b3 release of CAR-engineered cells after contact with PSCA-positive target cells. YTS cells modified with DAP12 alone or with a CAR bearing a phosphorylation-defective ITAM were not activated. Notably, infused YTS cells armed with anti\u2013PSCA-DAP12 caused delayed tumor xenograft growth and resulted in complete tumor eradication in a significant fraction of treated mice. The feasibility of the DAP12-based CAR was further tested in human primary NK cells and confers specific cytotoxicity against KIR\/HLA-matched PSCA-positive tumor cells, which was further enhanced by KIR-HLA mismatches. We conclude that NK cells engineered with DAP12-based CARs are a promising tool for adoptive tumor immunotherapy.<\/jats:p>","DOI":"10.4049\/jimmunol.1400330","type":"journal-article","created":{"date-parts":[[2015,3,4]],"date-time":"2015-03-04T21:32:44Z","timestamp":1425504764000},"page":"3201-3212","source":"Crossref","is-referenced-by-count":239,"title":["DAP12-Based Activating Chimeric Antigen Receptor for NK Cell Tumor Immunotherapy"],"prefix":"10.1093","volume":"194","author":[{"given":"Katrin","family":"T\u00f6pfer","sequence":"first","affiliation":[{"name":"Section of Experimental Neurosurgery and Tumor Immunology, Department of Neurosurgery, University Hospital Carl Gustav Carus , TU Dresden, 01307 Dresden ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marc","family":"Cartellieri","sequence":"additional","affiliation":[{"name":"Institute of Radiopharmaceutical Cancer Research, Helmholtz-Zentrum Dresden-Rossendorf , 01328 Dresden ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Susanne","family":"Michen","sequence":"additional","affiliation":[{"name":"Section of Experimental Neurosurgery and Tumor Immunology, Department of Neurosurgery, University Hospital Carl Gustav Carus , TU Dresden, 01307 Dresden ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ralf","family":"Wiedemuth","sequence":"additional","affiliation":[{"name":"Section of Experimental Neurosurgery and Tumor Immunology, Department of Neurosurgery, University Hospital Carl Gustav Carus , TU Dresden, 01307 Dresden ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nadja","family":"M\u00fcller","sequence":"additional","affiliation":[{"name":"Section of Experimental Neurosurgery and Tumor Immunology, Department of Neurosurgery, University Hospital Carl Gustav Carus , TU Dresden, 01307 Dresden ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dirk","family":"Lindemann","sequence":"additional","affiliation":[{"name":"Institute of Virology, Medical Faculty Carl Gustav Carus , TU Dresden, 01307 Dresden ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Bachmann","sequence":"additional","affiliation":[{"name":"Institute of Radiopharmaceutical Cancer Research, Helmholtz-Zentrum Dresden-Rossendorf , 01328 Dresden ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Monika","family":"F\u00fcssel","sequence":"additional","affiliation":[{"name":"DKMS Life Science Lab, GmbH , 01307 Dresden ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gabriele","family":"Schackert","sequence":"additional","affiliation":[{"name":"Section of Experimental Neurosurgery and Tumor Immunology, Department of Neurosurgery, University Hospital Carl Gustav Carus , TU Dresden, 01307 Dresden ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Achim","family":"Temme","sequence":"additional","affiliation":[{"name":"Section of Experimental Neurosurgery and Tumor Immunology, Department of Neurosurgery, University Hospital Carl Gustav Carus , TU Dresden, 01307 Dresden ,","place":["Germany"]},{"name":"German Cancer Consortium (DKTK) , 01307 Dresden ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2015,4,1]]},"reference":[{"key":"2025030705364143600_r1","doi-asserted-by":"crossref","first-page":"95ra73","DOI":"10.1126\/scitranslmed.3002842","article-title":"T cells with chimeric antigen receptors have potent antitumor effects and can establish memory in patients with advanced leukemia","volume":"3","author":"Kalos","year":"2011","journal-title":"Sci. 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