{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T17:25:28Z","timestamp":1785432328531,"version":"3.56.0"},"posted":{"date-parts":[[2026,4,14]]},"group-title":"Synthetic Biology","reference-count":67,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2026,4,14]],"date-time":"2026-04-14T00:00:00Z","timestamp":1776124800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"id":[{"id":"https:\/\/ror.org\/02c6k8737","id-type":"ROR","asserted-by":"publisher"}]},{"award":["P50CA126752"],"award-info":[{"award-number":["P50CA126752"]}],"id":[{"id":"https:\/\/ror.org\/040gcmg81","id-type":"ROR","asserted-by":"publisher"}]},{"id":[{"id":"https:\/\/ror.org\/0003xa228","id-type":"ROR","asserted-by":"publisher"}]},{"id":[{"id":"https:\/\/ror.org\/00k6e3143","id-type":"ROR","asserted-by":"publisher"}]},{"id":[{"id":"https:\/\/ror.org\/038ja4880","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2026,4,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:p>\n                  Chimeric antigen receptor (CAR)-modified V\u03b42 T cells are an attractive therapeutic cell platform for cancer immunotherapy. However, their clinical efficacy is limited by short\n                  <jats:italic>in vivo<\/jats:italic>\n                  persistence due to insufficient cytokine support and high susceptibility to activation-induced cell death (AICD). Through comparison of membrane-bound (mb) cytokines, we identified mbIL-18 to support superior anti-tumor activity of CAR-V\u03b42 T cells\n                  <jats:italic>in vitro<\/jats:italic>\n                  and\n                  <jats:italic>in vivo<\/jats:italic>\n                  . To reduce constitutive surface exposure of IL-18 and enable antigen-driven signal 3, we fused MyD88 - the key IL-18R signaling mediator - to an extracellular domain of Fas (Fas88). Antigen stimulation-induced FasL engagement of Fas88 triggered IL-18 signaling while simultaneously protecting V\u03b42 T cells from AICD. Fas88-armed human CAR-V\u03b42 T cells produced superior yet stimulation-dependent\n                  <jats:italic>in vivo<\/jats:italic>\n                  expansion and functional persistence in xenograft models of hematologic and solid malignancies. Together, these findings highlight the importance of IL-18 signaling and AICD resistance for CAR-V\u03b42 T cell activity, enabling a single-transgene modification to limit inflammatory risk and facilitate clinical translation.\n                <\/jats:p>","DOI":"10.64898\/2026.04.13.717612","type":"posted-content","created":{"date-parts":[[2026,4,15]],"date-time":"2026-04-15T07:25:12Z","timestamp":1776237912000},"source":"Crossref","is-referenced-by-count":0,"title":["Engineering CAR-V\u03b42 T cells to boost persistence and anti-tumor function"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4420-3021","authenticated-orcid":false,"given":"Leonard","family":"Leong","sequence":"first","affiliation":[{"name":"Center for Cell and Gene Therapy, Baylor College of Medicine, Texas Children\u2019s Hospital and Houston Methodist Hospital, Houston, Texas, 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