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Abstract Glioblastoma (GBM) is a highly aggressive brain tumor with poor prognosis and limited treatment options. Chimeric antigen receptor T cell (CAR-T) therapy has emerged as a promising immunotherapy for GBM. However, unlike conventional drugs, CAR-T cells are living therapeutics that exhibit non-linear pharmacokinetics, expansion, and complex tissue trafficking, making conventional animal-to-human dose extrapolation unreliable.
Abstract Glioblastoma remains a challenging indication for immunotherapy: the blood-brain barrier hampers accessibility for systemic treatments and the immunosuppressive microenvironment impedes immune attack. Intratumoral therapy with the proinflammatory cytokine interleukin-12 (IL-12) can revert immunosuppression but leakage into the circulation causes treatment-limiting toxicity.
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