MODL-11. NOVEL IMMUNOTHERAPY MODEL IN AGGRESSIVE PEDIATRIC H3K27M MUTANT GLIOMAS WITH INDUCIBLE TGFBR2 AND LAG3 EXPRESSION

Abstract INTRODUCTION Gliomas are considered immunologically “cold” tumors that mask themselves from the immune system. Immunotherapy, a breakthrough for cancer treatment, remains inefficient gliomas. H3K27M mutant diffuse midline glioma has poor survival. Using our innovative mosaic analysis with dual recombinases technology (Cell 2019), we further created novel murine model of an inducible expression LAG3 and TGFBR2 to make tumor recognizable by This allows studying molecular mechanisms “perfect” immunotherapy in pediatric gliomas histone H3.3 mutations. METHODS To model, plasmids doxycycline-inducible were designed, sequenced, replicated. For vitro validation, neuronal stem cells nucleofected these plasmids, grown sorted. Doxycycline was added experimental group induce expression. The then electroporated into neonatal MGMT mice (n=21) both genders. Control used on standard diet (n=9) (n=12) given doxycycline food vivo. Mice followed up RESULTS Plasmid sequencing validation demonstrated their high purity. In showed significant increase immunofluorescent staining after addition doxycycline. mouse survival study benefit treatment surviving 46% longer (135 ± 41.9 days vs. 92.6 32.7 control group, p=0.030). Conclusion Future Directions: We have successfully modified simulate immunotherapy. benefit. development organoid transplants more uniform testing next-generation is ongoing. can lead emergence therapies uncover response treatment.