Phase 1 huCART19-IL18-eDHFR CD19 CAR-T secreting IL-18 with PET cell-tracking

This Phase 1, open-label, single-arm study from the University of Pennsylvania tests huCART19-IL18-eDHFR: an autologous, CD19-directed CAR T-cell therapy “armored” to secrete interleukin‑18 (IL‑18) to boost antitumor immune activity, plus an eDHFR reporter to enable in vivo imaging. Participants have relapsed/refractory follicular lymphoma grade 1–3A after at least 2 prior lines, with CD19 expression; the initial strategy is notable for omitting routine lymphodepletion in Arm A while giving a flat-dose infusion (with additional dose levels/arms possible by amendment). The translational core is PET/CT tracking of the engineered CAR T cells using the investigational tracer [18F]fluoropropyl‑trimethoprim ([18F]FP‑TMP), aiming to quantify CAR T pharmacokinetics, biodistribution, and persistence in patients rather than inferring them from blood alone. Scientifically, this pairs an IL‑18–secreting CAR design (building on prior huCART19‑IL18 clinical work at Penn) with a clinically actionable “where are the cells?” imaging readout that could de-risk dosing and help explain response/toxicity heterogeneity. For R/R follicular lymphoma after 2+ lines, current care typically cycles through anti‑CD20–based regimens and targeted options (e.g., lenalidomide‑rituximab, bispecific antibodies, and CD19 CAR T in appropriate candidates), and this explores a next-step CAR platform plus real-time trafficking assessment.