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Overcoming such toxic effects of anticancer cellular products is a potential critical barrier to the development of combined therapeutic approaches. We are evaluating an anticancer strategy that focuses on overcoming such a barrier by genetically engineering drug-resistant variants of immunocompetent cells, thereby allowing for the coadministration of cellular therapy with cytotoxic chemotherapy, a method we refer to as drug-resistant immunotherapy (DRI). The strategy relies on the use of cDNA sequences that confer drug resistance and recombinant lentiviral vectors to transfer nucleic acid sequences into immunocompetent cells. In the present study, we evaluated a DRI-based strategy that incorporates the immunocompetent cell line NK-92, which has intrinsic antitumor properties, genetically engineered to be resistant to both temozolomide and trimetrexate. These immune effector cells efficiently lysed neuroblastoma cell lines, which we show are also sensitive to both chemotherapy agents. The antitumor efficacy of the DRI strategy was demonstrated\n                    <jats:italic toggle=\"yes\">in vivo<\/jats:italic>\n                    , whereby neuroblastoma-bearing NOD\/SCID\/\u03b3-chain knockout (NSG) mice treated with dual drug-resistant NK-92 cell therapy followed by dual cytotoxic chemotherapy showed tumor regression and significantly enhanced survival compared with animals receiving either nonengineered cell-based therapy and chemotherapy, immunotherapy alone, or chemotherapy alone. These data show there is a benefit to using drug-resistant cellular therapy when combined with cytotoxic chemotherapy approaches.\n                  <\/jats:p>","DOI":"10.1089\/hum.2011.172","type":"journal-article","created":{"date-parts":[[2012,3,7]],"date-time":"2012-03-07T13:46:00Z","timestamp":1331127960000},"page":"711-721","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":9,"title":["Treatment of a Solid Tumor Using Engineered Drug-Resistant Immunocompetent Cells and Cytotoxic Chemotherapy"],"prefix":"10.1177","volume":"23","author":[{"given":"Anindya","family":"Dasgupta","sequence":"first","affiliation":[{"name":"Emory University School of Medicine"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jordan E.","family":"Shields","sequence":"additional","affiliation":[{"name":"Emory University School of Medicine"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"H. 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Antitumor activity of temozolomide combined with irinotecan is partly independent of O6-methylguanine-DNA methyltransferase and mismatch repair phenotypes in xenograft models. Clin. Cancer Res., 6:4110\u20134118.","journal-title":"Clin. Cancer Res."},{"key":"e_1_3_3_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1465-3249(05)70785-4"},{"key":"e_1_3_3_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jim.2007.06.013"},{"key":"e_1_3_3_25_1","doi-asserted-by":"publisher","DOI":"10.1038\/mt.2011.1"},{"key":"e_1_3_3_26_1","doi-asserted-by":"publisher","DOI":"10.1002\/pbc.22855"},{"key":"e_1_3_3_27_1","first-page":"1952","article-title":"In vivo selection of hematopoietic progenitor cells and temozolomide dose intensification in rhesus macaques through lentiviral transduction with a drug resistance gene","volume":"119","author":"Larochelle A.","year":"2009","unstructured":"Larochelle A., , Choi U., , Shou Y. et al. 2009. 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