The foundation of precision immunotherapy in oncology is rooted in computational biology and patient-derived sample sequencing to enrich for and target immunogenic epitopes. Discovery of these tumor-specific epitopes through tumor sequencing has revolutionized patient outcomes in many types of cancers that were previously untreatable. However, these therapeutic successes are far from universal, especially with cancers that carry high intratumoral heterogeneity such as glioblastoma (GBM). Herein, we present the technical aspects of Mannan-BAM, TLR Ligands, Anti-CD40 Antibody (MBTA) vaccine immunotherapy, an investigational therapeutic that potentially circumvents the need for in silico tumor-neoantigen enrichment. We then review the most promising GBM vaccination strategies to contextualize the MBTA vaccine. By reviewing current evidence using translational tumor models supporting MBTA vaccination, we evaluate the underlying principles that validate its clinical applicability. Finally, we showcase the translational potential of MBTA vaccination as a potential immunotherapy in GBM, along with established surgical and immunologic cancer treatment paradigms.

Department of Medical Biology University of South Bohemia Cheske Budejovice 37005 Czech Republic

Department of Neurosurgery Medstar Georgetown Hospital Washington DC 20007 USA

Department of Neurosurgery University of Nebraska Medical Center Omaha NE 68198 USA

Neuro Oncology Branch National Cancer Institute National Institutes of Health Bethesda MD 20892 USA

Section on Medical Neuroendocrinology NICHD DIR National Institutes of Health Bethesda MD 20892 USA

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