{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T05:49:25Z","timestamp":1790660965240,"version":"4.1.0"},"reference-count":47,"publisher":"SAGE Publications","issue":"7-8","license":[{"start":{"date-parts":[[2020,4,1]],"date-time":"2020-04-01T00:00:00Z","timestamp":1585699200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2020,4,1]],"date-time":"2020-04-01T00:00:00Z","timestamp":1585699200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Human Gene Therapy"],"published-print":{"date-parts":[[2020,4]]},"abstract":"<jats:p>\n                    Human cytomegalovirus (HCMV) reactivations are associated with lower overall survival after transplantations. Adoptive transfer of HCMV-reactive expanded or selected T cells can be applied as a compassionate use, but requires that the human leukocyte antigen-matched donor provides memory cells against HCMV. To overcome this, we developed engineered T cells expressing chimeric antigen receptors (CARs) targeted against the HCMV glycoprotein B (gB) expressed upon viral reactivation. Single-chain variable fragments (scFvs) derived from a human high-affinity gB-specific neutralizing monoclonal antibody (SM5-1) were fused to CARs with 4-1BB (BBL) or CD28 (28S) costimulatory domains and subcloned into retroviral vectors. CD4\n                    <jats:sup>+<\/jats:sup>\n                    and CD8\n                    <jats:sup>+<\/jats:sup>\n                    T cells obtained from HCMV-seronegative adult blood or cord blood (CB) transduced with the vectors efficiently expressed the gB-CARs. The specificity and potency of gB-CAR-T cells were demonstrated and compared\n                    <jats:italic toggle=\"yes\">in vitro<\/jats:italic>\n                    using the following: 293T cells expressing gB, and with mesenchymal stem cells infected with a HCMV TB40 strain expressing\n                    <jats:italic toggle=\"yes\">Gaussia<\/jats:italic>\n                    luciferase (HCMV\/GLuc). BBL-gB-CAR-T cells generated with adult or CB demonstrated significantly higher\n                    <jats:italic toggle=\"yes\">in vitro<\/jats:italic>\n                    activation and cytotoxicity performance than 28-gB-CAR-T cells.\n                    <jats:uri xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"http:\/\/Nod.Rag.Gamma\">Nod.Rag.Gamma<\/jats:uri>\n                    (NRG) mice transplanted with human CB CD34\n                    <jats:sup>+<\/jats:sup>\n                    cells with long-term human immune reconstitution were used to model HCMV\/GLuc infection\n                    <jats:italic toggle=\"yes\">in vivo<\/jats:italic>\n                    by optical imaging analyses. One week after administration, response to BBL-gB-CAR-T cell therapy was observed for 5\/8 mice, defined by significant reduction of the bioluminescent signal in relation to untreated controls. Response to therapy was sporadically associated with CAR detection in spleen. Thus, exploring scFv derived from the high-affinity gB-antibody SM5-1 and the 4-1BB signaling domain for CAR design enabled an\n                    <jats:italic toggle=\"yes\">in vitro<\/jats:italic>\n                    high on-target effect and cytotoxicity and encouraging results\n                    <jats:italic toggle=\"yes\">in vivo<\/jats:italic>\n                    . Therefore, gB-CAR-T cells can be a future clinical option for treatment of HCMV reactivations, particularly when memory T cells from the donors are not available.\n                  <\/jats:p>","DOI":"10.1089\/hum.2019.149","type":"journal-article","created":{"date-parts":[[2020,3,11]],"date-time":"2020-03-11T09:19:51Z","timestamp":1583918391000},"page":"423-439","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":40,"title":["Adult and Cord Blood-Derived High-Affinity gB-CAR-T Cells Effectively React Against Human Cytomegalovirus Infections"],"prefix":"10.1177","volume":"31","author":[{"given":"Henning","family":"Olbrich","sequence":"first","affiliation":[{"name":"Laboratory of Regenerative Immune Therapies Applied, Department of Hematology, Hemostasis, Oncology and Stem Cell Transplantation, Hannover Medical School, Hannover, Germany."},{"name":"German Center for Infection Research (DZIF), Partner Site Hannover-Braunschweig, Braunschweig, Germany."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sebastian J.","family":"Theobald","sequence":"additional","affiliation":[{"name":"Laboratory of Regenerative Immune Therapies Applied, Department of Hematology, Hemostasis, Oncology and Stem Cell Transplantation, Hannover Medical School, Hannover, Germany."},{"name":"German Center for Infection Research (DZIF), Partner Site Hannover-Braunschweig, Braunschweig, Germany."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Constanze","family":"Slabik","sequence":"additional","affiliation":[{"name":"Laboratory of Regenerative Immune Therapies Applied, Department of Hematology, Hemostasis, Oncology and Stem Cell Transplantation, Hannover Medical School, Hannover, Germany."},{"name":"German Center for Infection Research (DZIF), Partner Site Hannover-Braunschweig, Braunschweig, Germany."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura","family":"Gerasch","sequence":"additional","affiliation":[{"name":"Laboratory of Regenerative Immune Therapies Applied, Department of Hematology, Hemostasis, Oncology and Stem Cell Transplantation, Hannover Medical School, Hannover, Germany."},{"name":"German Center for Infection Research (DZIF), Partner Site Hannover-Braunschweig, Braunschweig, Germany."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andreas","family":"Schneider","sequence":"additional","affiliation":[{"name":"Laboratory of Regenerative Immune Therapies Applied, Department of Hematology, Hemostasis, Oncology and Stem Cell Transplantation, Hannover Medical School, Hannover, Germany."},{"name":"German Center for Infection Research (DZIF), Partner Site Hannover-Braunschweig, Braunschweig, Germany."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Mach","sequence":"additional","affiliation":[{"name":"Institute for Clinical and Molecular Virology, Friedrich-Alexander-Universit\u00e4t Erlangen-N\u00fcrnberg, Erlangen, Germany."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas","family":"Shum","sequence":"additional","affiliation":[{"name":"Center for Cell and Gene Therapy, Baylor College of Medicine, Houston, Texas."},{"name":"Medical Scientist Training Program, Baylor College of Medicine, Houston, Texas."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maksim","family":"Mamonkin","sequence":"additional","affiliation":[{"name":"Center for Cell and Gene Therapy, Baylor College of Medicine, Houston, Texas."},{"name":"Department of Pathology and Immunology, Baylor College of Medicine, Houston, Texas."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Renata","family":"Stripecke","sequence":"additional","affiliation":[{"name":"Laboratory of Regenerative Immune Therapies Applied, Department of Hematology, Hemostasis, Oncology and Stem Cell Transplantation, Hannover Medical School, Hannover, Germany."},{"name":"German Center for Infection Research (DZIF), Partner Site Hannover-Braunschweig, Braunschweig, Germany."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","published-online":{"date-parts":[[2020,4,16]]},"reference":[{"key":"e_1_3_6_2_2","doi-asserted-by":"publisher","DOI":"10.1097\/QCO.0000000000000375"},{"key":"e_1_3_6_3_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2013-05-499830"},{"key":"e_1_3_6_4_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2015-11-679639"},{"key":"e_1_3_6_5_2","first-page":"7","article-title":"Prevention and treatment of cytomegalovirus infection and disease after bone marrow transplantation in the 1990s","volume":"8","author":"Winston DJ","year":"1991","unstructured":"Winston DJ, , Gale RP. 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