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

Abstract

Abstract 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.