{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,1]],"date-time":"2026-06-01T23:53:06Z","timestamp":1780357986775,"version":"3.54.1"},"reference-count":32,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2022,4,29]],"date-time":"2022-04-29T00:00:00Z","timestamp":1651190400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100005189","name":"Leukemia and Lymphoma Society","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100005189","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p>Virus-specific T cells (VSTs) are an attractive cell therapy platform for the delivery of tumor-targeted transgenic receptors. However, manufacturing with conventional methods may require several weeks and intensive handling. Here we evaluated the feasibility and timelines when combining IFN-\u03b3 cytokine capture (CC) with retroviral transduction for the generation of T cell receptor (TCR) and CD8\u03b1\u03b2 (TCR8) transgenic VSTs to simultaneously target several viral and tumor antigens in a single\u00a0product.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Healthy donor peripheral blood mononuclear cells were stimulated with cytomegalovirus (CMV) and Epstein-Barr-Virus (EBV) peptide mixtures derived from immunogenic viral proteins, followed by CC bead selection. After 3 days in culture, cells were transduced with a retroviral vector encoding four genes (a survivin-specific \u03b1\u03b2TCR and CD8\u03b1\u03b2). TCR8-transgenic or control VSTs were expanded and characterized for their phenotype, specificity and anti-viral and anti-tumor functions.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>CC selected cells were efficiently transduced with TCR8. Average fold expansion was 269-fold in 10 days, and cells contained a high proportion of CD8+ T central memory cells. TCR8+ VSTs simultaneously expressed native anti-viral and transgenic anti-survivin TCRs on their cell surface. Both control and TCR8+ VSTs produced cytokines to and killed viral targets, while tumor targets were only recognized and killed by TCR8+ VSTs.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>IFN-\u03b3 cytokine capture selects and activates CMV and EBV-specific memory precursor CD8+ T cells that can be efficiently gene-modified by retroviral transduction and rapidly <jats:italic>ex vivo<\/jats:italic> expanded. Our multi-specific T cells are polyfunctional and recognize and kill viral and leukemic targets expressing the cognate antigens.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fimmu.2022.830021","type":"journal-article","created":{"date-parts":[[2022,4,29]],"date-time":"2022-04-29T07:33:51Z","timestamp":1651217631000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":4,"title":["Rapid Generation of TCR and CD8\u03b1\u03b2 Transgenic Virus Specific T Cells for Immunotherapy of Leukemia"],"prefix":"10.3389","volume":"13","author":[{"given":"Gagan","family":"Bajwa","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Caroline","family":"Arber","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2022,4,29]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2016-01-628982","article-title":"T Cells for Viral Infections After Allogeneic Hematopoietic Stem Cell Transplant","volume":"127","author":"Bollard","year":"2016","journal-title":"Blood"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1038\/s41409-019-0614-1","article-title":"Therapeutic Advantages Provided by Banked Virus-Specific T-Cells of Defined HLA-Restriction","volume":"54","author":"O'Reilly","year":"2019","journal-title":"Bone Marrow 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