eligibility_summary
Adults 18–70 with R/R CD19+ B‑cell NHL (DLBCL, PMBCL, TFL, HGBCL, FL, MCL[t(11,14)/cyclin D1], MZL), measurable disease, ECOG ≤2, adequate organ function. Prior: anti‑CD20+anthracycline, MCL also BTKi, transformed FL R/R post‑transformation. Exclude: OS<3 mo, recent auto‑SCT (<3 mo) or any allo‑SCT, prior CD19/CAR‑T, recent chemo/biologics/radiation, CNS disease, active HIV/HBV/HCV/EBV/CMV, major cardiac/cNS disorders, autoimmune/immunodeficiency, recent VTE, vaccine ≤6 wks, urgent therapy, hypersensitivity, noncompliance.
trial_source
clinical_trials.gov from Dec 2, 2025
annotation_status
ai
ai_summary
Interventions: ATHENA—CRISPR-edited, allogeneic, second-generation anti‑CD19 CAR‑T (FMC63 scFv, CD28 hinge/transmembrane and costimulatory domain, CD3ζ signaling) plus lymphodepleting fludarabine (purine analog) and cyclophosphamide (alkylating agent). Mechanisms: CAR‑T binds CD19 to drive T-cell–mediated cytotoxicity, TRAC knockout removes endogenous TCR to reduce graft‑versus‑host disease, SPPL3 (Power3) knockout reprograms Golgi glycosylation (“glycan shielding”) to lessen alloimmune recognition and improve persistence, fludarabine/cyclophosphamide deplete host lymphocytes to enable CAR expansion. Targets: CD19+ malignant B cells, TCR pathway (TRAC), glycosylation pathway (SPPL3), host lymphocyte compartment.