Mannan-BAM, TLR Ligands, Anti-CD40 Antibody (MBTA) Vaccine Immunotherapy: A Review of Current Evidence and Applications in Glioblastoma

Lookian, Pashayar P.; Zhao, David; Medina, Rogelio; Wang, Herui; Zenka, Jan; Gilbert, Mark R.; Pacák, Karel; Zhuang, Zhengping

doi:10.3390/ijms22073455

Cited by 8 publications

(7 citation statements)

References 37 publications

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“…Most of the current immunotherapy trends are heavily oriented toward the onset of adaptive immunity via immunomodulators like TLR agonists. Here we present a new immunotherapeutic approach developed by our research group based on autologous tumor neoantigens and TLR agonists that are proficient in triggering both the innate and adaptive immune responses ( 199 , 200 ). It’s an autologous vaccine strategy that leverages the PRR assets of TLRs as well as fungal polysaccharides, and it has been tested in diverse types of mouse tumor models ( 11 , 14 , 199 – 201 ).…”

Section: Application Of Tlr Agonists As Adjuvants Of Cancer Vaccinementioning

confidence: 99%

Application of toll-like receptors (TLRs) and their agonists in cancer vaccines and immunotherapy

Chakraborty,

Ye,

Wang

et al. 2023

Front. Immunol.

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Toll-like receptors (TLRs) are pattern recognition receptors (PRRs) expressed in various immune cell types and perform multiple purposes and duties involved in the induction of innate and adaptive immunity. Their capability to propagate immunity makes them attractive targets for the expansion of numerous immunotherapeutic approaches targeting cancer. These immunotherapeutic strategies include using TLR ligands/agonists as monotherapy or combined therapeutic strategies. Several TLR agonists have demonstrated significant efficacy in advanced clinical trials. In recent years, multiple reports established the applicability of TLR agonists as adjuvants to chemotherapeutic drugs, radiation, and immunotherapies, including cancer vaccines. Cancer vaccines are a relatively novel approach in the field of cancer immunotherapy and are currently under extensive evaluation for treating different cancers. In the present review, we tried to deliver an inclusive discussion of the significant TLR agonists and discussed their application and challenges to their incorporation into cancer immunotherapy approaches, particularly highlighting the usage of TLR agonists as functional adjuvants to cancer vaccines. Finally, we present the translational potential of rWTC-MBTA vaccination [irradiated whole tumor cells (rWTC) pulsed with phagocytic agonists Mannan-BAM, TLR ligands, and anti-CD40 agonisticAntibody], an autologous cancer vaccine leveraging membrane-bound Mannan-BAM, and the immune-inducing prowess of TLR agonists as a probable immunotherapy in multiple cancer types.

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Section: Application Of Tlr Agonists As Adjuvants Of Cancer Vaccinementioning

confidence: 99%

Application of toll-like receptors (TLRs) and their agonists in cancer vaccines and immunotherapy

Chakraborty,

Ye,

Wang

et al. 2023

Front. Immunol.

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“…For example, convection-enhanced delivery [74]. Generally, combination approaches have shown the most potential therapeutic value of CD40 agonist antibodies or other CD40-targeting approaches in combination with other immunestimulating or conventional treatments in preclinical studies to date [75][76][77][78][79]. This may also partly reflect induction of inflammation (and therefore more targets) by one of the combination agents, e.g., IFNγ and LPS induction of CD40 [72][73][74]80].…”

Section: Further Molecular Targets and Myeloid Cell Relevancementioning

confidence: 99%

Challenges and Opportunities for Immunotherapeutic Intervention against Myeloid Immunosuppression in Glioblastoma

Exley

Garcia²,

Zellander³

et al. 2022

JCM

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Glioblastoma multiforme (GBM), the most common and deadly brain cancer, exemplifies the paradigm that cancers grow with help from an immunosuppressive tumor microenvironment (TME). In general, TME includes a large contribution from various myeloid lineage-derived cell types, including (in the brain) altered pathogenic microglia as well as monocyte-macrophages (Macs), myeloid-derived suppressor cells (MDSC) and dendritic cell (DC) populations. Each can have protective roles, but has, by definition, been coopted by the tumor in patients with progressive disease. However, evidence demonstrates that myeloid immunosuppressive activities can be reversed in different ways, leading to enthusiasm for this therapeutic approach, both alone and in combination with potentially synergistic immunotherapeutic and other strategies. Here, we review the current understanding of myeloid cell immunosuppression of anti-tumor responses as well as potential targets, challenges, and developing means to reverse immunosuppression with various therapeutics and their status. Targets include myeloid cell colony stimulating factors (CSFs), insulin-like growth factor 1 (IGF1), several cytokines and chemokines, as well as CD40 activation and COX2 inhibition. Approaches in clinical development include antibodies, antisense RNA-based drugs, cell-based combinations, polarizing cytokines, and utilizing Macs as a platform for Chimeric Antigen Receptors (CAR)-based tumor targeting, like with CAR-T cells. To date, promising clinical results have been reported with several of these approaches.

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“…When used as a vaccine adjuvant, this polymer can enhance the immune response, especially against the human immunodeficiency virus (HIV) [103]. Other promising applications, for which mannan-based delivery systems have been investigated, include glioblastoma therapy [106], alternative medicine in lung cancer [107], and hypolipidemic medication [108].…”

Section: Other Natural Polymersmentioning

confidence: 99%

Polymer-Based Nanosystems—A Versatile Delivery Approach

Niculescu

Grumezescu

2021

Materials

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Polymer-based nanoparticles of tailored size, morphology, and surface properties have attracted increasing attention as carriers for drugs, biomolecules, and genes. By protecting the payload from degradation and maintaining sustained and controlled release of the drug, polymeric nanoparticles can reduce drug clearance, increase their cargo’s stability and solubility, prolong its half-life, and ensure optimal concentration at the target site. The inherent immunomodulatory properties of specific polymer nanoparticles, coupled with their drug encapsulation ability, have raised particular interest in vaccine delivery. This paper aims to review current and emerging drug delivery applications of both branched and linear, natural, and synthetic polymer nanostructures, focusing on their role in vaccine development.

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Mannan-BAM, TLR Ligands, Anti-CD40 Antibody (MBTA) Vaccine Immunotherapy: A Review of Current Evidence and Applications in Glioblastoma

Cited by 8 publications

References 37 publications

Application of toll-like receptors (TLRs) and their agonists in cancer vaccines and immunotherapy

Application of toll-like receptors (TLRs) and their agonists in cancer vaccines and immunotherapy

Challenges and Opportunities for Immunotherapeutic Intervention against Myeloid Immunosuppression in Glioblastoma

Polymer-Based Nanosystems—A Versatile Delivery Approach

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