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.

• Keywords
• T cell, Toll-like receptor, Toll-like receptor ligands, adaptive immunity, anti-CD40, glioblastoma, immunotherapy, innate immunity, mannan-BAM, metastatic, neutrophil, pathogen-associated molecular patterns,
• MeSH
• Antigen-Presenting Cells chemistry   MeSH
• CD40 Antigens immunology   MeSH
• Epitopes chemistry   MeSH
• Glioblastoma immunology   therapy   MeSH
• Immunophenotyping MeSH
• Immunotherapy methods   MeSH
• Medical Oncology trends   MeSH
• Humans MeSH
• Ligands MeSH
• Neoplasm Metastasis MeSH
• Mice MeSH
• Brain Neoplasms immunology   therapy   MeSH
• Peptides chemistry   MeSH
• Cancer Vaccines MeSH
• Computational Biology MeSH
• Treatment Outcome MeSH
• Animals MeSH
• Check Tag
• Humans MeSH
• Mice MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH
• Review MeSH
• Names of Substances
• CD40 Antigens MeSH
• Epitopes MeSH
• Ligands MeSH
• Peptides MeSH
• Cancer Vaccines MeSH

Emerging evidence is demonstrating the extent of T-cell infiltration within the tumor microenvironment has favorable prognostic and therapeutic implications. Hence, immunotherapeutic strategies that augment the T-cell signature of tumors hold promising therapeutic potential. Recently, immunotherapy based on intratumoral injection of mannan-BAM, toll-like receptor ligands and anti-CD40 antibody (MBTA) demonstrated promising potential to modulate the immune phenotype of injected tumors. The strategy promotes the phagocytosis of tumor cells to facilitate the recognition of tumor antigens and induce a tumor-specific adaptive immune response. Using a syngeneic colon carcinoma model, we demonstrate MBTA's potential to augment CD8+ T-cell tumor infiltrate when administered intratumorally or subcutaneously as part of a whole tumor cell vaccine. Both immunotherapeutic strategies proved effective at controlling tumor growth, prolonged survival and induced immunological memory against the parental cell line. Collectively, our investigation demonstrates MBTA's potential to trigger a potent anti-tumor immune response.

• Keywords
• TLR, adjuvant, immunogenic tumor cell vaccine, irradiation,
• Publication type
• Journal Article MeSH