Phase 1 RNA-LP vaccine: CMV pp65–LAMP mRNA + autologous tumor mRNA immunotherapy

This first-in-human Phase 1, open-label, dose-escalation study at the University of Florida tests the manufacturing feasibility, safety, and maximum tolerated dose of an intravenous RNA–lipid particle (RNA-LP) cancer vaccine in pediatric patients with recurrent/progressive medulloblastoma after prior radiation. The investigational product packages two mRNA components in DOTAP lipid particles: (1) autologous total tumor mRNA (personalized tumor-antigen source) and (2) CMV pp65 fused to full-length LAMP (pp65–flLAMP) mRNA to enhance antigen routing/presentation and broaden T-cell priming. Mechanistically, the lipid particles deliver mRNA to antigen-presenting cells, which translate the encoded antigens and present them to stimulate tumor-directed T-cell responses; the pp65 choice leverages the controversial-but-pursued CMV antigen strategy in brain tumors. University of Florida is the sponsor/owner of the investigational RNA-LP approach in this protocol. For children with recurrent medulloblastoma post-radiation, current care is largely palliative and trial-driven—salvage chemotherapy, re-irradiation when feasible, and selected surgery—so a personalized IV mRNA vaccine is an attempt to add a tolerable immune option where durable responses are uncommon.