{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,21]],"date-time":"2026-07-21T22:45:24Z","timestamp":1784673924976,"version":"3.55.0"},"reference-count":43,"publisher":"MDPI AG","issue":"21","license":[{"start":{"date-parts":[[2023,10,31]],"date-time":"2023-10-31T00:00:00Z","timestamp":1698710400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"CPRIT RP160283-Baylor College of Medicine Comprehensive Cancer Training Program","award":["NIH-NCI P50 CA126752"],"award-info":[{"award-number":["NIH-NCI P50 CA126752"]}]},{"name":"CPRIT RP160283-Baylor College of Medicine Comprehensive Cancer Training Program","award":["NIH-NLBI-HHSN268201600015I"],"award-info":[{"award-number":["NIH-NLBI-HHSN268201600015I"]}]},{"name":"American Society of Gene and Cell Therapy (ASGCT) Career Development Award 2019","award":["NIH-NCI P50 CA126752"],"award-info":[{"award-number":["NIH-NCI P50 CA126752"]}]},{"name":"American Society of Gene and Cell Therapy (ASGCT) Career Development Award 2019","award":["NIH-NLBI-HHSN268201600015I"],"award-info":[{"award-number":["NIH-NLBI-HHSN268201600015I"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>The efficacy of therapeutic T-cells is limited by a lack of positive signals and excess inhibitory signaling in tumor microenvironments. We previously showed that a constitutively active IL7 receptor (C7R) enhanced the persistence, expansion, and anti-tumor activity of T-cells expressing chimeric antigen receptors (CARs), and C7R-modified GD2.CAR T-cells are currently undergoing clinical trials. To determine if the C7R could also enhance the activity of T-cells recognizing tumors via their native T-cell receptors (TCRs), we evaluated its effects in Epstein\u2013Barr virus (EBV)-specific T-cells (EBVSTs) that have produced clinical benefits in patients with EBV-associated malignancies. EBVSTs were generated by stimulation of peripheral blood T-cells with overlapping peptide libraries spanning the EBV lymphoma antigens, LMP1, LMP2, and EBNA 1, followed by retroviral vector transduction to express the C7R. The C7R increased STAT5 signaling in EBVSTs and enhanced their expansion over 30 days of culture in the presence or absence of exogenous cytokines. C7R-EBVSTs maintained EBV antigen specificity but were dependent on TCR stimulation for continued expansion. C7R-EBVSTs produced more rapid lymphoma control in a murine xenograft model than unmodified EBVSTs and persisted for longer. The findings have led to a clinical trial, evaluating C7R-EBVSTs for the treatment of refractory or relapsed EBV-positive lymphoma (NCT04664179).<\/jats:p>","DOI":"10.3390\/ijms242115806","type":"journal-article","created":{"date-parts":[[2023,10,31]],"date-time":"2023-10-31T11:16:27Z","timestamp":1698750987000},"page":"15806","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Constitutive Interleukin-7 Cytokine Signaling Enhances the Persistence of Epstein\u2013Barr Virus-Specific T-Cells"],"prefix":"10.3390","volume":"24","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9183-1894","authenticated-orcid":false,"given":"Sandhya","family":"Sharma","sequence":"first","affiliation":[{"name":"Graduate Program in Translational Biology and Molecular Medicine, Baylor College of Medicine, Houston, TX 77030, USA"},{"name":"Center for Cell and Gene Therapy, Texas Children\u2019s Hospital, Baylor College of Medicine, Houston, TX 77030, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tim","family":"Sauer","sequence":"additional","affiliation":[{"name":"Center for Cell and Gene Therapy, Texas Children\u2019s Hospital, Baylor College of Medicine, Houston, TX 77030, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bilal A.","family":"Omer","sequence":"additional","affiliation":[{"name":"Center for Cell and Gene Therapy, Texas Children\u2019s Hospital, Baylor College of Medicine, Houston, TX 77030, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas","family":"Shum","sequence":"additional","affiliation":[{"name":"Graduate Program in Translational Biology and Molecular Medicine, Baylor College of Medicine, Houston, TX 77030, USA"},{"name":"Center for Cell and Gene Therapy, Texas Children\u2019s Hospital, Baylor College of Medicine, Houston, TX 77030, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lisa A.","family":"Rollins","sequence":"additional","affiliation":[{"name":"Center for Cell and Gene Therapy, Texas Children\u2019s Hospital, Baylor College of Medicine, Houston, TX 77030, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cliona M.","family":"Rooney","sequence":"additional","affiliation":[{"name":"Center for Cell and Gene Therapy, Texas Children\u2019s Hospital, Baylor College of Medicine, Houston, TX 77030, USA"},{"name":"Department of Pediatrics, Section of Hematology-Oncology, Baylor College of Medicine, Houston, TX 77030, USA"},{"name":"Department of Molecular Virology and Microbiology, Baylor College of Medicine, Houston, TX 77030, USA"},{"name":"Department of Pathology-Immunology, Baylor College of Medicine, Houston, TX 77030, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,10,31]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"757","DOI":"10.1038\/nrc1452","article-title":"Epstein\u2013Barr Virus: 40 Years On","volume":"4","author":"Young","year":"2004","journal-title":"Nat. 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