IMMU-23. RESEARCH ON MULTI-ANTIGEN T CELL INFUSION AGAINST NEURO-ONCOLOGIC DISEASE (ReMIND)

INTRODUCTION: Pediatric patients with recurrent or progressive central nervous system (CNS) tumors have poor prognoses and clearly require improved therapies. Previous studies that used ex vivo expanded T cells show promising efficacy against viral infections. The polyclonal nature of these T cells, capable of recognizing multiple antigens, can be of potential benefit to patients with high-risk brain tumors, where intratumoral heterogeneity plays a prominent role in therapeutic resistance. METHODS: Patients with CNS malignancies received T cells in a phase I dose escalation study (NCT03652545). The safety and feasibility of infusing ex vivo expanded, autologous T cells was determined in patients with newly diagnosed diffuse intrinsic pontine gliomas (DIPGs, Arm A, infused up to 5 months post irradiation) or recurrent/progressive non-brainstem CNS malignancies with (Arm C) or without (Arm B) lymphodepletion. RESULTS: As of April 2023, 46 patients were enrolled on study. A total of 30 patients received infusions (8 in Arm A, 18 in Arm B, 4 in Arm C) that were well tolerated. One patient experienced a severe potentially-related adverse event (tumor swelling). In Arm A (DIPG), median OS was 12 months post-diagnosis (one patient survived for 31 months). In arm B, median OS was 11 months post T cell infusion, with 6 patients still alive (longest four years after treatment). In Arm C, 3/4 patients remain alive 4+ months from infusion (one patient had a potential pseudoprogression based on scans). CONCLUSIONS: Autologous T cells can be expanded from pediatric patients with CNS malignancies and are well tolerated. Data suggests that TAA-T products may induce an anti-tumor response, with or without lymphodepletion, and prolong survival. Efforts are ongoing to analyze immune correlates which are focused on evaluating circulating T cell clones and investigating changes in peripheral blood gene signatures and circulating plasma proteins.