{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,6]],"date-time":"2026-11-06T14:26:19Z","timestamp":1793975179657,"version":"4.8.0"},"reference-count":39,"publisher":"SAGE Publications","issue":"23-24","license":[{"start":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T00:00:00Z","timestamp":1791417600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"funder":[{"name":"Deutsche Krebshilfe","award":["#70114961"],"award-info":[{"award-number":["#70114961"]}],"id":[{"id":"https:\/\/ror.org\/01wxdd722","id-type":"ROR","asserted-by":"crossref"}]},{"name":"F\u00f6rderverein Knochenmarktransplantation in Hamburg e.V."},{"name":"Hamburgische Landesforschungsf\u00f6rderung","award":["Transiente CAR-Effektorzellen:neue Ans\u00e4tze zu ihr"],"award-info":[{"award-number":["Transiente CAR-Effektorzellen:neue Ans\u00e4tze zu ihr"]}]},{"name":"Deutsches Zentrum f\u00fcr Infektionsforschung","award":["Maternity Leave Stipend, TI 07.005_004"],"award-info":[{"award-number":["Maternity Leave Stipend, TI 07.005_004"]}],"id":[{"id":"https:\/\/ror.org\/028s4q594","id-type":"ROR","asserted-by":"crossref"}]},{"name":"Deutsches Zentrum f\u00fcr Infektionsforschung","award":["TTU HIV project TTU 04.819"],"award-info":[{"award-number":["TTU HIV project TTU 04.819"]}],"id":[{"id":"https:\/\/ror.org\/028s4q594","id-type":"ROR","asserted-by":"crossref"}]}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Human Gene Therapy"],"published-print":{"date-parts":[[2026,12,1]]},"abstract":"<jats:p>\n                    Adoptive transfer of gene-modified autologous T cells, for example, expressing chimeric antigen receptors (CARs), is a promising therapy option for a variety of malignant and nonmalignant diseases. Given their increased risk to develop certain cancer types, namely lymphoma, and the current progress with HIVenv-directed CARs, people living with HIV (PLWH) might particularly profit from CAR-T therapies. At the same time, clinical translation of novel advanced therapy medicinal products remains challenging, partly due to the elaborate\n                    <jats:italic toggle=\"yes\">ex vivo<\/jats:italic>\n                    production under good manufacturing practice (GMP) conditions. This holds especially true for T-cell products from PLWH, which require special manufacturing conditions to suppress HIV replication. We aimed to exemplarily address this limitation in the context of CD19-CAR-T cells for HIV-positive cancer patients. To this end, we developed an integrated, GMP-compliant process for lentiviral CAR transfer and simultaneous knockout of the HIV coreceptor C-C chemokine receptor 5 (CCR5) by mRNA electroporation of our transcription activator-like effector nuclease (CCR5-Uco-hetTALEN) based on the CliniMACS Prodigy. We successfully performed three manufacturing runs to produce CCR5-edited CD19-CAR-T cells on a clinical scale, generating up to 3.9 \u00d7 10\n                    <jats:sup>9<\/jats:sup>\n                    viable T cells. Thirty-seven percent to 55% of the T cells in the final product expressed functional CD19-CARs, the overall CCR5 editing rates ranged from 42% to 54%. The third large-scale process was performed in the presence of the antiretroviral drug saquinavir to suppress potential viral replication during manufacturing of cells from HIV-positive patients. In summary, we have developed a GMP-compliant manufacturing process for gene-edited CAR-T cells under antiretroviral suppression, which might help to accelerate the translation of cellular immunotherapies, namely CAR-T cells for patients living with HIV in the future.\n                  <\/jats:p>","DOI":"10.1177\/10430342261492461","type":"journal-article","created":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T10:08:32Z","timestamp":1791454112000},"page":"1121-1129","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":0,"title":["Automated Production of Gene-Edited CAR-T Cells for People Living with HIV"],"prefix":"10.1177","volume":"37","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2201-1910","authenticated-orcid":false,"given":"Lea Isabell","family":"Schwarze","sequence":"first","affiliation":[{"name":"Department of Stem Cell Transplantation, Research Department Cell and Gene Therapy, University Medical Centre, Hamburg, Germany"},{"name":"German Centre for Infection Research (DZIF), partner site Hamburg-L\u00fcbeck-Borstel-Riems, Hamburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Niklas","family":"Nuppenau","sequence":"additional","affiliation":[{"name":"Department of Stem Cell Transplantation, Research Department Cell and Gene Therapy, University Medical Centre, Hamburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jan Hendrik","family":"M\u00fcller","sequence":"additional","affiliation":[{"name":"Department of Stem Cell Transplantation, Research Department Cell and Gene Therapy, University Medical Centre, Hamburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Almut","family":"Uhde","sequence":"additional","affiliation":[{"name":"Department of Stem Cell Transplantation, Research Department Cell and Gene Therapy, University Medical Centre, Hamburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nahla","family":"Al Ashkar","sequence":"additional","affiliation":[{"name":"Department of Stem Cell Transplantation, Research Department Cell and Gene Therapy, University Medical Centre, Hamburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tanja","family":"Schr\u00f6der","sequence":"additional","affiliation":[{"name":"Department of Stem Cell Transplantation, Research Department Cell and Gene Therapy, University Medical Centre, Hamburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kristoffer","family":"Riecken","sequence":"additional","affiliation":[{"name":"Department of Stem Cell Transplantation, Research Department Cell and Gene Therapy, University Medical Centre, Hamburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Boris","family":"Fehse","sequence":"additional","affiliation":[{"name":"Department of Stem Cell Transplantation, Research Department Cell and Gene Therapy, University Medical Centre, Hamburg, Germany"},{"name":"German Centre for Infection Research (DZIF), partner site Hamburg-L\u00fcbeck-Borstel-Riems, Hamburg, Germany"},{"name":"German Centre for Child and Adolescent Health (DZKJ), Hamburg, Germany."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","published-online":{"date-parts":[[2026,10,8]]},"reference":[{"issue":"8","key":"e_1_3_3_2_1","article-title":"The role of CAR T-cell therapy in relapsed\/refractory adult B-ALL","volume":"22","author":"Othman T","year":"2024","unstructured":"1.Othman T, , Logan AC, , Muffly L, et al. The role of CAR T-cell therapy in relapsed\/refractory adult B-ALL. JNCCN Journal of the National Comprehensive Cancer Network 2024;22(8).","journal-title":"JNCCN Journal of the National Comprehensive Cancer Network"},{"key":"e_1_3_3_3_1","article-title":"A guide to CAR T cell therapies: Development, current status and future prospects","author":"Rafei H","unstructured":"2.Rafei H, , Upadhyay R, , Sharma P. A guide to CAR T cell therapies: Development, current status and future prospects. Nat Rev Immunol 2026; ahead of print.","journal-title":"Nat Rev Immunol 2026; ahead of print"},{"key":"e_1_3_3_4_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41434-021-00246-w"},{"key":"e_1_3_3_5_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41434-024-00446-0"},{"key":"e_1_3_3_6_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms241411803"},{"key":"e_1_3_3_7_1","unstructured":"6.CHMP. Aucatzyl; INN-obecabtagene autoleucel CHMP; 2026. 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