EPCT-15. THE REMIND TRIAL: MULTI-ANTIGEN TARGETED T CELLS FOR PEDIATRIC CNS TUMORS

Abstract BACKGROUND Patients with relapsed CNS malignancies or DIPG face terrible prognoses. We hypothesized that T cells specific for 3 tumor-associated antigens (TAA), WT1, PRAME and survivin, would be safe and elicit anti-tumor immunity. METHODS Patients (n=9) have received autologous tumor antig...

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Published inNeuro-oncology (Charlottesville, Va.) Vol. 22; no. Supplement_3; p. iii306
Main Authors Grant, Melanie, Fortiz, Maria Fernanda, Wang, Lu, Lang, Haili, Datar, Anushree, Reynolds, Emily, Terpilowski, Madeline, Lazarski, Chris, Tanna, Jay, Pitino, Adriana, Zhang, Nan, Hoq, Fahmida, Hanley, Patrick, Kilburn, Lindsay, Packer, Roger, Rood, Brian, Bollard, Catherine, Hwang, Eugene
Format Journal Article
LanguageEnglish
Published US Oxford University Press 04.12.2020
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Summary:Abstract BACKGROUND Patients with relapsed CNS malignancies or DIPG face terrible prognoses. We hypothesized that T cells specific for 3 tumor-associated antigens (TAA), WT1, PRAME and survivin, would be safe and elicit anti-tumor immunity. METHODS Patients (n=9) have received autologous tumor antigen-associated T cells (TAAT) (up to 4x107/m2) for newly diagnosed DIPG (Group A) or recurrent CNS malignancies (Group B) on a Phase I dose-escalation study (NCT03652545) and were monitored for safety and response. RESULTS/ DISCUSSION 9/9 patients who received TAAT completed the 45-day safety monitoring phase with no dose-limiting toxicities. Infused cells were predominantly CD3+ T cells (median 96%; range: 87–99%), with CD4+ and CD8+ comprising 16% (range: 5–87%) and 40% (range: 4–67%) of the CD3+ cells, respectively. TAAT with specificity for 1–3 TAAs, at varying frequencies, was demonstrated in 8/9 TAAT by anti-IFN-γ ELISPOT. Plasma cytokine profiles demonstrated infusion-related immune cytokine responses. In summary, TAAT are safe and may elicit anti-tumor responses in vivo. To confirm TAAT-driven effects, we are evaluating plasma proteomic profiles for immune-response signatures and assessing unique T cell receptor rearrangements of infused TAAT. Response assessment and dose escalation are ongoing.
ISSN:1522-8517
1523-5866
DOI:10.1093/neuonc/noaa222.137