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.

• MeSH
• antigen prezentující buňky chemie   MeSH
• antigeny CD40 imunologie   MeSH
• epitopy chemie   MeSH
• glioblastom imunologie   terapie   MeSH
• imunofenotypizace MeSH
• imunoterapie metody   MeSH
• lékařská onkologie trendy   MeSH
• lidé MeSH
• ligandy MeSH
• metastázy nádorů MeSH
• myši MeSH
• nádory mozku imunologie   terapie   MeSH
• peptidy chemie   MeSH
• protinádorové vakcíny MeSH
• výpočetní biologie MeSH
• výsledek terapie MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH

Toll-like receptors (TLR) are key components of innate immune system. As TLR activation could induce potentially harmful inflammatory response, activation of TLR signaling pathways has to be under tight control. Besides other control mechanisms, an inhibitory function of murine TLR4 splice variants was recently demonstrated. In this study we investigated expression of four TLR4 splice variants in human antigen presenting cells (APC). Furthermore, we studied modification in TLR4 splice variants expression in APC in cystic fibrosis (CF) patients chronically infected by Gram-negative bacteria. We developed a novel reliable real-time PCR detection system that allowed monitoring of individual TLR4 splice variants expression. In APC from healthy donors we detected a characteristic transient increase of two out of four splice variants after lipopolysaccharide (LPS) stimulation. Similarly to murine TLR4, one of these variants, NM 003266, might translate to a potentially inhibitory protein. In contrast to controls, CF monocytes had significantly changed LPS-induced expression of TLR4 gene and its variants including reduced ability to up-regulate the expression of the potentially inhibitory variant upon stimulation. In accordance with this observation, monocytes from CF patients produced significantly more tumor necrosis factor after LPS stimulation than healthy controls. Our results thus describe the kinetics of TLR4 splicing variants expression after LPS stimulation and indicate a possible alteration of its regulation in CF patients.

• MeSH
• alternativní sestřih MeSH
• antigen prezentující buňky chemie   imunologie   MeSH
• cystická fibróza imunologie   MeSH
• dendritické buňky imunologie   MeSH
• dospělí MeSH
• financování organizované MeSH
• kultivované buňky MeSH
• lidé MeSH
• lipopolysacharidy imunologie   MeSH
• messenger RNA analýza   MeSH
• monocyty imunologie   MeSH
• polymerázová řetězová reakce s reverzní transkripcí metody   MeSH
• regulace genové exprese MeSH
• stanovení celkové genové exprese MeSH
• TNF-alfa biosyntéza   MeSH
• toll-like receptor 4 biosyntéza   genetika   MeSH
• Check Tag
• dospělí MeSH
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH