RNA Vaccination Drives Expansion and Brain-Licensing of T Cells to Enhance the Efficacy of Adoptive Cell Therapy in Glioblastoma.

mRNA vaccination encoding SIINFEKL drives OT1 CD8+ T cell expansion to up to 80% of circulating CD8+ T cells and improves brain infiltration in glioma models.

• Why it matters: Adoptive TCR-T therapy is less effective in brain tumors because transferred T cells lack antigen access needed for restimulation and persistence.
• What they did: In glioma models, transferred ovalbumin-specific OT1 CD8+ T cells were restimulated in vivo using mRNA delivered to splenic dendritic cells encoding the immunodominant MHC class I epitope SIINFEKL.
• The result: RNA vaccination markedly increased T cell infiltration, retained an interferon-stimulated gene signature in the brain, and suppressed glioblastoma growth, supporting mRNA boosting of TCR-T therapy.

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