{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T11:22:04Z","timestamp":1790162524944,"version":"4.1.0"},"reference-count":46,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2016,6,11]],"date-time":"2016-06-11T00:00:00Z","timestamp":1465603200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","award":["GRK1172"],"award-info":[{"award-number":["GRK1172"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Intl Journal of Cancer"],"published-print":{"date-parts":[[2016,10,15]]},"abstract":"<jats:p>Pre\u2010emptive cancer immunotherapy by donor lymphocyte infusion (DLI) using cytokine\u2010induced killer (CIK) cells may be beneficial to prevent relapse with a reduced risk of causing graft\u2010<jats:italic>versus<\/jats:italic>\u2010host\u2010disease. CIK cells are a heterogeneous effector cell population including T cells (CD3<jats:sup>+<\/jats:sup> CD56<jats:sup>\u2212<\/jats:sup>), natural killer (NK) cells (CD3<jats:sup>\u2212<\/jats:sup>CD56<jats:sup>+<\/jats:sup>) and natural killer T (T\u2010NK) cells (CD3<jats:sup>+<\/jats:sup> CD56<jats:sup>+<\/jats:sup>) that exhibit non\u2010major histocompatibility complex (MHC)\u2010restricted cytotoxicity and are generated by <jats:italic>ex vivo<\/jats:italic> expansion of peripheral blood mononuclear cells in the presence of interferon (IFN)\u2010\u03b3, anti\u2010CD3 antibody, interleukin\u20102 (IL\u20102) and interleukin\u201015 (IL\u201015). To facilitate selective target\u2010cell recognition and enhance specific cytotoxicity against B\u2010cell acute lymphoblastic leukemia (B\u2010ALL), we transduced CIK cells with a lentiviral vector encoding a chimeric antigen receptor (CAR) that carries a composite CD28\u2010CD3\u03b6 domain for signaling and a CD19\u2010specific scFv antibody fragment for cell binding (CAR 63.28.z). <jats:italic>In vitro<\/jats:italic> analysis revealed high and specific cell killing activity of CD19\u2010targeted CIK\/63.28.z cells against otherwise CIK\u2010resistant cancer cell lines and primary B\u2010ALL blasts, which was dependent on CD19 expression and CAR signaling. In a xenograft model in immunodeficient mice, treatment with CIK\/63.28.z cells in contrast to therapy with unmodified CIK cells resulted in complete and durable molecular remissions of established primary pre\u2010B\u2010ALL. Our results demonstrate potent antileukemic activity of CAR\u2010engineered CIK cells <jats:italic>in vitro<\/jats:italic> and <jats:italic>in vivo<\/jats:italic>, and suggest this strategy as a promising approach for adoptive immunotherapy of refractory pre\u2010B\u2010ALL.<\/jats:p>","DOI":"10.1002\/ijc.30217","type":"journal-article","created":{"date-parts":[[2016,6,2]],"date-time":"2016-06-02T17:07:39Z","timestamp":1464887259000},"page":"1799-1809","source":"Crossref","is-referenced-by-count":57,"title":["Chimeric antigen receptor\u2010engineered cytokine\u2010induced killer cells overcome treatment resistance of pre\u2010B\u2010cell acute lymphoblastic leukemia and enhance survival"],"prefix":"10.1002","volume":"139","author":[{"given":"Sarah","family":"Oelsner","sequence":"first","affiliation":[{"name":"Georg\u2010Speyer\u2010Haus Institute for Tumor Biology and Experimental Therapy Frankfurt Germany"},{"name":"Division for Stem Cell Transplantation and Immunology Hospital for Children and Adolescents, Goethe University Frankfurt Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juliane","family":"Wagner","sequence":"additional","affiliation":[{"name":"Division for Stem Cell Transplantation and Immunology Hospital for Children and Adolescents, Goethe University Frankfurt Germany"},{"name":"LOEWE Center for Cell and Gene Therapy Goethe University Frankfurt Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Miriam E.","family":"Friede","sequence":"additional","affiliation":[{"name":"Georg\u2010Speyer\u2010Haus Institute for Tumor Biology and Experimental Therapy Frankfurt Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Verena","family":"Pfirrmann","sequence":"additional","affiliation":[{"name":"Division for Stem Cell Transplantation and Immunology Hospital for Children and Adolescents, Goethe University Frankfurt Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sabrina","family":"Gen\u00dfler","sequence":"additional","affiliation":[{"name":"Georg\u2010Speyer\u2010Haus Institute for Tumor Biology and Experimental Therapy Frankfurt Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eva","family":"Rettinger","sequence":"additional","affiliation":[{"name":"Division for Stem Cell Transplantation and Immunology Hospital for Children and Adolescents, Goethe University Frankfurt Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christian J.","family":"Buchholz","sequence":"additional","affiliation":[{"name":"Molecular Biotechnology and Gene Therapy Paul\u2010Ehrlich\u2010Institut Langen Germany"},{"name":"German Cancer Consortium (DKTK) Heidelberg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Heike","family":"Pfeifer","sequence":"additional","affiliation":[{"name":"Department of Medicine, Hematology and Oncology Goethe University Frankfurt Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ralf","family":"Schubert","sequence":"additional","affiliation":[{"name":"Division for Allergology, Pneumology and Cystic Fibrosis Hospital for Children and Adolescents, Goethe University Frankfurt Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Oliver G.","family":"Ottmann","sequence":"additional","affiliation":[{"name":"Department of Haematology, Division of Cancer and Genetics Cardiff University School of Medicine Cardiff United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Evelyn","family":"Ullrich","sequence":"additional","affiliation":[{"name":"Division for Stem Cell Transplantation and Immunology Hospital for Children and Adolescents, Goethe University Frankfurt Germany"},{"name":"LOEWE Center for Cell and Gene Therapy Goethe University Frankfurt Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter","family":"Bader","sequence":"additional","affiliation":[{"name":"Division for Stem Cell Transplantation and Immunology Hospital for Children and Adolescents, Goethe University Frankfurt Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Winfried S.","family":"Wels","sequence":"additional","affiliation":[{"name":"Georg\u2010Speyer\u2010Haus Institute for Tumor Biology and Experimental Therapy Frankfurt Germany"},{"name":"German Cancer Consortium (DKTK), Partner Site Frankfurt\/Mainz  Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2016,6,11]]},"reference":[{"key":"e_1_2_6_2_1","doi-asserted-by":"publisher","DOI":"10.1309\/AJCPAN7BH5DNYWZB"},{"key":"e_1_2_6_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbmt.2008.11.009"},{"key":"e_1_2_6_4_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2014.58.9747"},{"key":"e_1_2_6_5_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2008-03-077974"},{"key":"e_1_2_6_6_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2010-01-262089"},{"key":"e_1_2_6_7_1","doi-asserted-by":"publisher","DOI":"10.1517\/14712590903005552"},{"key":"e_1_2_6_8_1","doi-asserted-by":"publisher","DOI":"10.3109\/14653249.2011.613931"},{"key":"e_1_2_6_9_1","doi-asserted-by":"publisher","DOI":"10.3324\/haematol.2015.138016"},{"key":"e_1_2_6_10_1","doi-asserted-by":"publisher","DOI":"10.1084\/jem.174.1.139"},{"key":"e_1_2_6_11_1","doi-asserted-by":"publisher","DOI":"10.1023\/A:1015415928521"},{"key":"e_1_2_6_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jcyt.2015.04.011"},{"key":"e_1_2_6_13_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00432-014-1864-3"},{"key":"e_1_2_6_14_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1215134"},{"key":"e_1_2_6_15_1","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.3005930"},{"key":"e_1_2_6_16_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2013-06-506741"},{"key":"e_1_2_6_17_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1407222"},{"key":"e_1_2_6_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(14)61403-3"},{"key":"e_1_2_6_19_1","doi-asserted-by":"publisher","DOI":"10.1038\/icb.1991.58"},{"key":"e_1_2_6_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0161-5890(97)00144-2"},{"key":"e_1_2_6_21_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00262-012-1212-x"},{"key":"e_1_2_6_22_1","doi-asserted-by":"publisher","DOI":"10.1038\/mt.2014.219"},{"key":"e_1_2_6_23_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1106152"},{"key":"e_1_2_6_24_1","doi-asserted-by":"publisher","DOI":"10.1002\/ijc.28585"},{"key":"e_1_2_6_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.exphem.2008.11.002"},{"key":"e_1_2_6_26_1","doi-asserted-by":"publisher","DOI":"10.1089\/10430340252898984"},{"key":"e_1_2_6_27_1","doi-asserted-by":"publisher","DOI":"10.1038\/nbt0997-871"},{"key":"e_1_2_6_28_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2012-11-468579"},{"key":"e_1_2_6_29_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.leu.2403135"},{"key":"e_1_2_6_30_1","doi-asserted-by":"publisher","DOI":"10.3324\/haematol.2009.019885"},{"key":"e_1_2_6_31_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.bjc.6690800"},{"key":"e_1_2_6_32_1","doi-asserted-by":"publisher","DOI":"10.1002\/hon.886"},{"key":"e_1_2_6_33_1","doi-asserted-by":"publisher","DOI":"10.1155\/2013\/195691"},{"key":"e_1_2_6_34_1","doi-asserted-by":"publisher","DOI":"10.1155\/2014\/897214"},{"key":"e_1_2_6_35_1","doi-asserted-by":"publisher","DOI":"10.3324\/haematol.11132"},{"key":"e_1_2_6_36_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbmt.2011.05.012"},{"key":"e_1_2_6_37_1","doi-asserted-by":"publisher","DOI":"10.1002\/hon.1012"},{"key":"e_1_2_6_38_1","doi-asserted-by":"publisher","DOI":"10.1097\/CJI.0000000000000001"},{"key":"e_1_2_6_39_1","doi-asserted-by":"crossref","first-page":"1687","DOI":"10.4049\/jimmunol.153.4.1687","article-title":"A novel population of expanded human CD3+CD56+ cells derived from T cells with potent in vivo antitumor activity in mice with severe combined immunodeficiency","volume":"153","author":"Lu PH","year":"1994","journal-title":"J Immunol"},{"key":"e_1_2_6_40_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jcyt.2014.01.003"},{"key":"e_1_2_6_41_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.exphem.2006.05.004"},{"key":"e_1_2_6_42_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.exphem.2007.05.018"},{"key":"e_1_2_6_43_1","doi-asserted-by":"publisher","DOI":"10.1155\/2012\/238924"},{"key":"e_1_2_6_44_1","doi-asserted-by":"publisher","DOI":"10.1038\/mt.2013.192"},{"key":"e_1_2_6_45_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0952-7915(00)00094-7"},{"key":"e_1_2_6_46_1","doi-asserted-by":"publisher","DOI":"10.1097\/PPO.0000000000000035"},{"key":"e_1_2_6_47_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2003-06-2125"}],"container-title":["International Journal of Cancer"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fijc.30217","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/ijc.30217","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,3]],"date-time":"2023-10-03T13:44:31Z","timestamp":1696340671000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/ijc.30217"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2016,6,11]]},"references-count":46,"journal-issue":{"issue":"8","published-print":{"date-parts":[[2016,10,15]]}},"alternative-id":["10.1002\/ijc.30217"],"URL":"https:\/\/doi.org\/10.1002\/ijc.30217","archive":["Portico"],"relation":{},"ISSN":["0020-7136","1097-0215"],"issn-type":[{"value":"0020-7136","type":"print"},{"value":"1097-0215","type":"electronic"}],"subject":[],"published":{"date-parts":[[2016,6,11]]}}}