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The monoclonal antibody (mAb) trastuzumab has improved the outcomes of patients with HER2+ breast cancer. However, a large number of HER2+ tumors are not responsive to, or become resistant to, trastuzumab-based therapy, and thus more effective therapies targeting HER2 are needed.<\/jats:p>\n                     <\/jats:sec><jats:sec>\n                        <jats:title>Methods<\/jats:title>\n                        <jats:p>HER2-specific T cells were generated by the transfer of genes that encode chimeric antigen receptor (CAR). Using a multistep overlap extension PCR method, we constructed a novel, humanized HER2 CAR-containing, chA21 single-chain variable fragment (scFv) region of antigen-specific mAb and T-cell intracellular signaling chains made up of CD28 and CD3\u03b6. An interferon \u03b3 and interleukin 2 enzyme-linked immunosorbent assay and a chromium-51 release assay were used to evaluate the antitumor immune response of CAR T cells in coculture with tumor cells. Furthermore, SKBR3 tumor\u2013bearing nonobese diabetic\/severe combined immunodeficiency (NOD\/SCID) mice were treated with HER2 CAR T cells to evaluate antitumor activity. Human CD3+ T cell accumulation in tumor xenograft was detected by immunohistochemistry.<\/jats:p>\n                     <\/jats:sec><jats:sec>\n                        <jats:title>Results<\/jats:title>\n                        <jats:p>chA21-28z CAR was successfully constructed, and both CD4+ and CD8+ T cells were transduced. The expanded HER2 CAR T cells expressed a central memory phenotype and specifically reacted against HER2+ tumor cell lines. Furthermore, the SKBR3 tumor xenograft model revealed that HER2 CAR T cells significantly inhibited tumor growth <jats:italic>in vivo<\/jats:italic>. Immunohistochemical analysis showed robust accumulation of human CD3+ T cells in regressing SKBR3 lesions.<\/jats:p>\n                     <\/jats:sec><jats:sec>\n                        <jats:title>Conclusions<\/jats:title>\n                        <jats:p>The results of this study show that novel chA21 scFv-based, HER2-specific CAR T cells not only recognized and killed HER2+ breast and ovarian cancer cells <jats:italic>ex vivo<\/jats:italic> but also induced regression of experimental breast cancer <jats:italic>in vivo<\/jats:italic>. Our data support further exploration of the HER2 CAR T-cell therapy for HER2-expressing cancers.<\/jats:p>\n                     <\/jats:sec>","DOI":"10.1186\/bcr3674","type":"journal-article","created":{"date-parts":[[2014,6,11]],"date-time":"2014-06-11T11:05:43Z","timestamp":1402484743000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":102,"title":["Construction and evaluation of a novel humanized HER2-specific chimeric receptor"],"prefix":"10.1186","volume":"16","author":[{"given":"Meili","family":"Sun","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huan","family":"Shi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chuanyong","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jie","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xianqiang","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuping","family":"Sun","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2014,6,11]]},"reference":[{"key":"3417_CR1","doi-asserted-by":"publisher","first-page":"16","DOI":"10.1038\/nrclinonc.2011.177","volume":"9","author":"CL Arteaga","year":"2011","unstructured":"Arteaga CL, Sliwkowski MX, Osborne CK, Perez EA, Puglisi F, Gianni L: Treatment of HER2-positive breast cancer: current status and future perspectives. 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