WT1/PRAME/survivin trivalent TAA‑T cells show tolerable safety and rare long remissions in pediatric CNS tumors

ReMIND (NCT03652545) tested autologous, non–gene-engineered multi-antigen tumor-associated antigen–specific T cells (TAA‑Ts) targeting intracellular WT1, PRAME, and survivin, given systemically in an open-label Phase 1 adaptive dose-finding study across three pediatric CNS tumor cohorts: newly diagnosed diffuse intrinsic pontine glioma (DIPG) without lymphodepletion (arm A; 16 enrolled/11 infused) and relapsed/recurrent nonbrainstem CNS tumors without (arm B; 28 enrolled/18 infused) or with lymphodepletion (arm C; 7 enrolled/4 infused). The maximum tolerated dose was dose level 3 (8×10^7 cells/m^2/dose); most common AEs were fatigue and headache, but tumor swelling occurred (2 possibly related SAEs) including one grade 5 dose-limiting toxicity in DIPG with hydrocephalus/edema/respiratory failure—an on-target “inflammation in a closed box” risk that’s less typical with chemo SOC. Efficacy signals were modest on medians (arm A median OS 13.7 months from diagnosis—around the ~8–12 month median OS commonly reported with radiotherapy-based DIPG SOC; arms B/C median PFS 5.0 months from infusion), but notable tail outcomes emerged in relapse: 3 arm B/C patients remained alive without disease at 31.8, 41.2, and 51.6 months (including 1 complete response), which is uncommon in most recurrent pediatric CNS tumor settings where durable disease-free survival is rare and highly histology-dependent.