IMMU-03. IDENTIFICATION OF GENETIC BIOMARKERS TO PREDICT RESPONSE TO HSV-1 G207 AND POLIO:RHINOVIRUS IMMUNOTHERAPY

Abstract BACKGROUND The polio:rhinovirus chimera, PVSRIPO, and the herpes simplex virus, G207, are viral immunotherapies with promising results in Phase I trials of pediatric high-grade glioma (pHGG) medulloblastoma. While some patients have durable responses, others no benefit. purpose this study is to identify genes that putatively confer resistance immunotherapy. METHODS A panel medulloblastoma pHGG cell lines were treated either PVSRIPO or G207 categorized into “sensitive” “resistant” groups based viability. Flow cytometry was used quantify receptor expression (CD111 for CD155 PVSRIPO). RNA sequencing completed on resistant sensitive cells. RESULTS D341 D556 had < 50% viability at 72h (G207) 24h (PVSRIPO) as sensitive; D283 D324 resistant. There a correlation between CD111 (Spearman r=0.71) but number significantly differentially expressed (DE) (adjusted p≤0.05) higher compared medulloblastoma, both enriched (mean 666.4±614 vs. 454.6±377.4, P=0.0422) depleted (826.9±645.5 449±367.8, P=0.0167) after treatment. few shared DE cells G207: GCLM, LANCL2, RBM3 while ADAMTS1 VEGFA depleted. Likewise, there GPSM2, CHECK2, SEPTIN2, EIF4G2, GDAP1, PWP1. CONCLUSIONS Genetic analysis demonstrates minimal overlap two immunotherapies. PVRIPO infection resulted more gene GCLM LANCL2 by pHGG. These may serve potential biomarkers predicting response