{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,9]],"date-time":"2026-07-09T05:15:09Z","timestamp":1783574109302,"version":"3.55.0"},"reference-count":37,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,7,9]],"date-time":"2026-07-09T00:00:00Z","timestamp":1783555200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100007557","name":"California Institute of Regenerative Medicine","doi-asserted-by":"publisher","award":["CLIN1-14840"],"award-info":[{"award-number":["CLIN1-14840"]}],"id":[{"id":"10.13039\/100007557","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:p>\n                    Type 1 regulatory T (Tr1) cells are IL-10\u2013producing CD4\n                    <jats:sup>+<\/jats:sup>\n                    regulatory T cells that play a central role in maintaining peripheral immune tolerance. Prior investigations of autologous Tr1 cell-based therapies have demonstrated clinical promise in graft-versus-host disease (GvHD), but widespread clinical application has been constrained by challenges in scaling cell production. TRX103 is an engineered, allogeneic Tr1 cell therapy manufactured using a fully compliant, current Good Manufacturing Practice-compatible process. TRX103 is generated by pooling engineered CD4\n                    <jats:sup>+<\/jats:sup>\n                    T cells from three healthy donors that have been transduced with a lentiviral vector encoding human IL-10 and a truncated human nerve growth factor receptor, CD271.\n                    <jats:italic>In vitro<\/jats:italic>\n                    , off-the-shelf TRX103 suppressed effector T cell proliferation and inhibited pro-inflammatory cytokine production by monocytes from both healthy donors and patients with Crohn\u2019s disease.\n                    <jats:italic>In vivo<\/jats:italic>\n                    , TRX103 homed to intestinal tissues and prevented disease development in a xenogeneic GvHD model. Phenotypic and functional analyses of TRX103 revealed the acquisition of a distinct cellular identity characterized by reduced expression of activation and immune synapse\u2013associated molecules and minimal allogeneic stimulatory capacity. Together, these findings define a distinct immunomodulatory profile for TRX103 and support its clinical development as a scalable allogeneic cell therapy for immune-mediated diseases. TRX103 is currently being evaluated in a Phase 1\/2a study in treatment-refractory Crohn\u2019s disease (NCT06721962) and a Phase I study for GvHD prevention in hematopoietic stem cell transplantation recipients (NCT06462365).\n                  <\/jats:p>","DOI":"10.3389\/fimmu.2026.1848770","type":"journal-article","created":{"date-parts":[[2026,7,9]],"date-time":"2026-07-09T04:23:20Z","timestamp":1783571000000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Engineering allogeneic type 1 regulatory T cells: a scalable, off-the-shelf platform for restoring immune tolerance"],"prefix":"10.3389","volume":"17","author":[{"given":"Molly Javier","family":"Uyeda","sequence":"first","affiliation":[{"name":"Tr1X Inc.","place":["San Diego, CA, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Audrey","family":"Re","sequence":"additional","affiliation":[{"name":"Tr1X Inc.","place":["San Diego, 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