{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,8]],"date-time":"2026-01-08T19:13:24Z","timestamp":1767899604398,"version":"3.49.0"},"reference-count":36,"publisher":"BMJ","issue":"2","license":[{"start":{"date-parts":[[2020,11,3]],"date-time":"2020-11-03T00:00:00Z","timestamp":1604361600000},"content-version":"unspecified","delay-in-days":2,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100004917","name":"Cancer Prevention and Research Institute of Texas","doi-asserted-by":"publisher","award":["Individual Investigator Research Award RP160345"],"award-info":[{"award-number":["Individual Investigator Research Award RP160345"]}],"id":[{"id":"10.13039\/100004917","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100013362","name":"Krebsforschung Schweiz","doi-asserted-by":"publisher","award":["KFS-4542-08-2018"],"award-info":[{"award-number":["KFS-4542-08-2018"]}],"id":[{"id":"10.13039\/501100013362","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100006392","name":"Centre Hospitalier Universitaire Vaudois","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100006392","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100005189","name":"Leukemia and Lymphoma Society","doi-asserted-by":"publisher","award":["6490-16"],"award-info":[{"award-number":["6490-16"]}],"id":[{"id":"10.13039\/100005189","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["bmj.com"],"crossmark-restriction":true},"short-container-title":["J Immunother Cancer"],"accepted":{"date-parts":[[2020,10,11]]},"published-print":{"date-parts":[[2020,11]]},"abstract":"<jats:sec>\n                  <jats:title>Background<\/jats:title>\n                  <jats:p>Genetically engineered virus-specific T cells (VSTs) are a platform for adoptive cell therapy after allogeneic hematopoietic stem cell transplantation. However, redirection to a tumor-associated antigen by the introduction of a transgenic T-cell receptor (TCR) reduces anti-viral activity, thereby impeding the possibility of preventing or treating two distinct complications\u2014malignant relapse and viral infection\u2014with a single cell therapy product. Availability of CD8\u03b1\u03b2 co-receptor molecules can significantly impact class I restricted T-cell activation, and thus, we interrogated whether transgenic CD8\u03b1\u03b2 improves anti-viral activity mediated by native VSTs with or without a co-expressed transgenic TCR (TCR8).<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>Our existing clinical VST manufacturing platform was adapted and validated to engineer TCR+ or TCR8+ VSTs targeting cytomegalovirus and Epstein-Barr virus. Simultaneous anti-viral and anti-tumor function of engineered VSTs was assessed in vitro and in vivo. We used pentamer staining, interferon (IFN)-\u03b3 enzyme-linked immunospot (ELISpot), intracellular cytokine staining (ICS), cytotoxicity assays, co-cultures, and cytokine secretion assays for the in vitro characterization. The in vivo anti-tumor function was assessed in a leukemia xenograft mouse model.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>Both transgenic CD8\u03b1\u03b2 alone and TCR8 had significant impact on the anti-viral function of engineered VSTs, and TCR8+ VSTs had comparable anti-viral activity as non-engineered VSTs as determined by IFN-\u03b3 ELISpot, ICS and cytotoxicity assays. TCR8-engineered VSTs had improved anti-tumor function and greater effector cytokine production in vitro, as well as enhanced anti-tumor function against leukemia xenografts in mice.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusion<\/jats:title>\n                  <jats:p>Incorporation of transgenic CD8\u03b1\u03b2 into vectors for TCR-targetable antigens preserves anti-viral activity of TCR transgenic VSTs while simultaneously supporting tumor-directed activity mediated by a transgenic TCR. Our approach may provide clinical benefit in preventing and treating viral infections and malignant relapse post-transplant.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1136\/jitc-2020-001487","type":"journal-article","created":{"date-parts":[[2020,11,4]],"date-time":"2020-11-04T03:25:26Z","timestamp":1604460326000},"page":"e001487","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":15,"title":["Transgenic CD8\u03b1\u03b2 co-receptor rescues endogenous TCR function in TCR-transgenic virus-specific T cells"],"prefix":"10.1136","volume":"8","clinical-trial-number":[{"clinical-trial-number":"nct01953900","registry":"10.18810\/clinical-trials-gov"}],"author":[{"given":"Gagan","family":"Bajwa","sequence":"first","affiliation":[{"name":"Department of Oncology UNIL CHUV, Lausanne University Hospital, Ludwig Institute for Cancer Research, University of Lausanne, Lausanne, Switzerland"},{"name":"Center for Cell and Gene Therapy, Baylor College of Medicine, Houston, Texas, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"In\u00e8s","family":"Lanz","sequence":"additional","affiliation":[{"name":"Department of Oncology UNIL CHUV, Lausanne University Hospital, Ludwig Institute for Cancer Research, University of Lausanne, Lausanne, Switzerland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mara","family":"Cardenas","sequence":"additional","affiliation":[{"name":"Center for Cell and Gene Therapy, Baylor College of Medicine, Houston, Texas, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Malcolm K","family":"Brenner","sequence":"additional","affiliation":[{"name":"Center for Cell and Gene Therapy, Baylor College of Medicine, Houston, Texas, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6440-9970","authenticated-orcid":false,"given":"Caroline","family":"Arber","sequence":"additional","affiliation":[{"name":"Department of Oncology UNIL CHUV, Lausanne University Hospital, Ludwig Institute for Cancer Research, University of Lausanne, Lausanne, Switzerland"},{"name":"Center for Cell and Gene Therapy, Baylor College of Medicine, Houston, Texas, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"239","published-online":{"date-parts":[[2020,11,3]]},"reference":[{"key":"2025100307504602000_8.2.e001487.1","unstructured":"D\u2019Souza A , Fretham C . 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Off-the-shelf allogeneic T cell therapies for cancer: opportunities and challenges using naturally occuring \u201cuniversal\u201d donor T cells. Front Immunol. 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