NUK - logo
E-viri
Celotno besedilo
Recenzirano
  • CTIM-25. EO2401 PEPTIDE IMM...
    Reardon, David; Idbaih, Ahmed; Vieito, Maria; Ghiringhelli, François; Stradella, Agostina; Tabatabai, Ghazaleh; Burger, Michael C; Mildenberger, Iris; Herrlinger, Ulrich; Wen, Patrick; Touat, Mehdi; Wick, Antje; González, Macarena; Hervieu, Alice; GilMartin, Marta; Renovanz, Mirjam; Gouttefangeas, Cécile; Maia, Ana; Bonny, Christophe; Paillarse, Jean-Michel; Chêne, Laurent; Fagerberg, Jan; Wick, Wolfgang

    Neuro-oncology (Charlottesville, Va.), 11/2023, Letnik: 25, Številka: Supplement_5
    Journal Article

    Abstract EO2401 expands existing memory T cells recognizing protein sequences from gut bacteria, which cross-react with tumor associated antigens (TAAs). EO2401 contains three CD8 HLA-A2 epitopes with mimicry to glioblastoma-TAAs (IL13Rα2, BIRC5, and FOXM1) and the CD4 epitope UCP2. Patients received EO2401 (300μg/peptide, q2weeks x4, then every 4weeks) with nivolumab (3mg/kg, q2weeks) in cohorts: C1a (n = 21, Ex2→EN; option for symptom directed low-dose bevacizumab sLDB; 5mg/kg, q2weeks as anti-edema treatment); C2a/1 (n = 23, EN); C2a/2 (n = 15, EN+sLDB); C2b (n = 6, adjuvant EN+sLDB); C2c (n = 9, neoadjuvant ENx2→surgery→adjuvant EN+sLDB); C3 (n = 26, EN+bevacizumab, q2weeks, 10mg/kg). EO2401/nivolumab+/-bevacizumab safety profile consistent with profile of nivolumab, and when applicable bevacizumab, except the addition of local administration site reactions which occurred in 39% of patients; 96% of events Grade 1/2 and 4% Grade 3. Immune monitoring (peripheral blood, ELISPOT, tetramer assessments) demonstrated expanded mimic specific CD8 T cells with cross-reactivity against the targeted human TAAs. In C2a/1 (83% tested) and in C3 (81% tested), 89% and 95% of tested patients showed expansion. Expansions were early (week 2 after starting EO2401), durable (up to 23 months), and robust (approximately 30% of all peripheral CD8 T cells were mimic specific in 3 clinical responders). In C2c, surgery specimens after two EO2401/nivolumab doses showed increased tumor T cell infiltration versus pre-treatment tumor in 5 of 6 patients. Addition of sLDB to EO2401/nivolumab prolonged treatment duration vs EO2401/nivolumab alone by reducing edema likely worsened by study therapy induced immune cell infiltration. Integration of bevacizumab with EO2401/nivolumab in C3 further increased efficacy in C3. C2a/1vsC2a/2vsC3: median treatment duration 1.4vs3.2vs4.8 months, disease control rate 22%vs40%vs88%, median PFS 1.6vs3.6vs5.5 months; median survival 9.0vs12.6vstoo early (C3 median FU 8.3 mo, survival ongoing up to 2 years). Further follow-up will be presented.