IMMU-12. NOVEL APPROACH FOR THE TREATMENT OF PEDIATRIC HIGH-GRADE GLIOMAS WITH THE COMBINATION OF ONCOLYTIC ADENOVIRUSES AND GENE THERAPY ENCODING A BiTE DIRECTED TO THE EphA2 TUMOR ANTIGEN

• Published in: Neuro-oncology (Charlottesville, Va.) Va.), 2019-04, Vol.21 (Supplement_2), p.ii95-ii95
• Main Authors: Arnone, Claudia Manuela, Belardinilli, Tamascia, Mastronuzzi, Angela, Polito, Vinicia, Cacchione, Antonella, Carai, Andrea, Camassei, Francesca Diomedi, Scarsella, Marco, Quintarelli, Concetta, Angelis, Biagio De, Locatelli, Franco, Caruana, Ignazio, Del Bufalo, Francesca
• Format: Article
• Language: English
• Subjects: Immunology/Immunotherapy
• ISSN: 1522-8517; 1523-5866
• DOI: 10.1093/neuonc/noz036.133

Abstract Pediatric high-grade gliomas (pHGG) are amongst the most common malignant neoplasms of childhood, whose outcome remains dismal with conventional treatments. New therapeutic approaches are urgently needed. Immunotherapy based on Oncolytic Adenovirus(OA)is a promising strategy but its efficacy is suboptimal. We aimed at improving the antitumor efficacy by combining the OA and a gene-therapy with the Bibispecific T-cell Engager (BiTE) directed towards the erythropoietin-producing human hepatocellular carcinoma A2-receptor (EphA2),conveyed by a replication-incompetent adenoviral vector (EAd). We demonstrated, by immunohistochemistry and qPCR, the expression of EphA2 in 100% (16/16) of the pHGGs, its intensity correlating significantly with a worst outcome. We then tested the transgene amplification, after co-infection, on two HGG cell lines (U373, U87) by qPCR and Flow Cytometry (FACS) for the selectable marker ∆CD19, confirming a significantly enhanced production in OA+EAd vs EAd alone (p