{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,23]],"date-time":"2026-06-23T11:08:52Z","timestamp":1782212932757,"version":"3.54.5"},"reference-count":43,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2018,10,26]],"date-time":"2018-10-26T00:00:00Z","timestamp":1540512000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100004484","name":"Tehran University of Medical Sciences and Health Services","doi-asserted-by":"publisher","award":["30381"],"award-info":[{"award-number":["30381"]}],"id":[{"id":"10.13039\/501100004484","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Journal Cellular Physiology"],"published-print":{"date-parts":[[2019,6]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Although remarkable results have been attained by adoptively transferring T\u00a0cells expressing fully murine and\/or humanized anti\u2010CD19 chimeric antigen receptors (CARs) to treat B cell malignancies, evidence of human anti\u2010mouse immune responses against CARs provides a rationale for the development of less immunogenic CARs. By developing a fully human CAR (huCAR), these human anti\u2010mouse immune responses are likely eliminated. This, perhaps, not only increases the persistence of anti\u2010CD19 CAR T\u00a0cells\u2014thereby reducing the risk of tumor relapse\u2014but also facilitates administration of multiple, temporally separated doses of CAR T\u00a0cells to the same recipient. To these ends, we have designed and constructed a second\u2010generation fully human anti\u2010CD19 CAR (or huCAR19) containing a fully human single\u2010chain variable fragment (ScFv) fused with a CD8a hinge, a 4\u20101BB transmembrane domain and intracellular T cell signaling domains of 4\u20101BB and CD3z. T\u00a0cells expressing this CAR specifically recognized and lysed CD19<jats:sup>+<\/jats:sup> target cells produced cytokines and proliferated in vitro. Moreover, cell volume data revealed that our huCAR construct cannot induce antigen\u2010independent tonic signaling in the absence of cognate antigen. Considering our results, our anti\u2010CD19 huCAR may overcome issues of transgene immunogenicity that plague trials utilizing CARs containing mouse\u2010derived ScFvs. These results suggest that this huCAR19 be safely and effectively applied for adaptive T cell immunotherapy in clinical practice.<\/jats:p>","DOI":"10.1002\/jcp.27599","type":"journal-article","created":{"date-parts":[[2018,10,26]],"date-time":"2018-10-26T10:44:19Z","timestamp":1540550659000},"page":"9207-9215","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":33,"title":["Construction and functional characterization of a fully human anti\u2010CD19 chimeric antigen receptor (huCAR)\u2010expressing primary human T\u00a0cells"],"prefix":"10.1002","volume":"234","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3303-2565","authenticated-orcid":false,"given":"Hamid Reza","family":"Mirzaei","sequence":"first","affiliation":[{"name":"Department of Medical Immunology School of Medicine, Tehran University of Medical Sciences Tehran Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arezoo","family":"Jamali","sequence":"additional","affiliation":[{"name":"Department of Molecular Medicine Faculty of Advanced Technologies in Medicine, Iran University of Medical Sciences Tehran Iran"},{"name":"Department of Medical Laboratory Sciences School of Allied Medical Sciences, Tehran University of Medical Sciences Tehran Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leila","family":"Jafarzadeh","sequence":"additional","affiliation":[{"name":"Department of Medical Immunology School of Medicine, Tehran University of Medical Sciences Tehran Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elham","family":"Masoumi","sequence":"additional","affiliation":[{"name":"Department of Medical Immunology School of Medicine, Tehran University of Medical Sciences Tehran Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Khadijeh","family":"Alishah","sequence":"additional","affiliation":[{"name":"Department of Biotechnology College of Science, University of Tehran Tehran Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Keyvan","family":"Fallah Mehrjardi","sequence":"additional","affiliation":[{"name":"Department of Medical Immunology School of Medicine, Tehran University of Medical Sciences Tehran Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Seyed Amir Hossein","family":"Emami","sequence":"additional","affiliation":[{"name":"Division of Oncology, Department of Internal Medicine School of Medicine, Tehran University of Medical Sciences Tehran Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Farshid","family":"Noorbakhsh","sequence":"additional","affiliation":[{"name":"Department of Medical Immunology School of Medicine, Tehran University of Medical Sciences Tehran Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brian G.","family":"Till","sequence":"additional","affiliation":[{"name":"Clinical Research Division Fred Hutchinson Cancer Research Center Seattle Washington"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8747-123X","authenticated-orcid":false,"given":"Jamshid","family":"Hadjati","sequence":"additional","affiliation":[{"name":"Department of Medical Immunology School of Medicine, Tehran University of Medical Sciences Tehran Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2018,10,26]]},"reference":[{"key":"e_1_2_8_1_2_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI46102"},{"key":"e_1_2_8_1_3_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2011-04-348540"},{"key":"e_1_2_8_1_4_1","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.3005930"},{"key":"e_1_2_8_1_5_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0082742"},{"key":"e_1_2_8_1_6_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2015.63.5904"},{"key":"e_1_2_8_1_7_1","doi-asserted-by":"publisher","DOI":"10.1038\/leu.2013.279"},{"key":"e_1_2_8_1_8_1","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.3008226"},{"key":"e_1_2_8_1_9_1","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-10-1280"},{"key":"e_1_2_8_1_10_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature21405"},{"issue":"6","key":"e_1_2_8_1_11_1","doi-asserted-by":"crossref","first-page":"2791","DOI":"10.4049\/jimmunol.161.6.2791","article-title":"Chimeric receptors providing both primary and costimulatory signaling in T\u00a0cells from a single gene product","volume":"161","author":"Finney H. 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