Intratumor injection of CCL21-coupled vault nanoparticles is associated with reduction in tumor volume in an in vivo model of glioma

Voth, Brittany; Pelargos, Panayiotis; Barnette, Natalie E.; Bhatt, Nikhilesh S.; Chen, Cheng Hao Jacky; Lagman, Carlito; Chung, Lawrance K.; Nguyen, Thien; Sheppard, John P.; Yang, Isaac; Mareninov, Sergey; Kickhoefer, Valerie A.; Yong, William H.; Rome, Leonard H.

doi:10.1007/s11060-020-03479-8

Cited by 23 publications

(20 citation statements)

References 30 publications

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“…According to this, the percentage of OVCAR-8 cells that become fluorescent due to GFP-INT internalization increases to approximately 12% and 24% after 2 and 4 h of incubation, respectively. This confirms the ability of vaults to enter cells (even without any specific cell targeting, as in our case) and thus, the well described functionality [16][17][18][19][20] of these nanocarriers as an efficient DDS.…”

Section: Gfp-int Cell Internalization Mediated By Recombinant Vaultssupporting

confidence: 88%

“…Taking into account all these properties, vaults have become one of the most promising nanovehicles as controlled DDS due to all their advantages (particle size, lumen large enough to encapsulate hundreds of protein molecules, protection of the cargo molecules from external proteases, biodegradability, biocompatibility, and non-immunogenicity). In this context, recombinant vaults have already been successfully explored for vaccination [16][17][18], proteins delivery [13,19], targeting of cell surface receptors [14] and delivery of therapeutics for lung cancer [16] or glioblastoma [20].…”

Section: Introductionmentioning

confidence: 99%

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All-in-one biofabrication and loading of recombinant vaults in human cells

et al. 2022

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One of the most promising approaches in the drug delivery field is the use of naturally occurring self-assembling protein nanoparticles, such as virus-like particles, bacterial microcompartments or vault ribonucleoprotein particles as drug delivery systems (DDS). Among them, eukaryotic vaults show a promising future due to their structural features, in vitro stability and non-immunogenicity. Recombinant vaults are routinely produced in insect cells and purified through several ultracentrifugations, both tedious and time-consuming processes. As an alternative, this work proposes a new approach and protocols for the production of recombinant vaults in human cells by transient gene expression of a His-tagged version of the Major Vault Protein (MVP-H6), the development of new affinity-based purification processes for such recombinant vaults, and the all-in-one biofabrication and encapsulation of a cargo recombinant protein within such vaults by their co-expression in human cells. Protocols proposed here allow the easy and straightforward biofabrication and purification of engineered vaults loaded with virtually any INT-tagged cargo protein, in very short times, paving the way to faster and easier engineering and production of better and more efficient DDS.

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Section: Gfp-int Cell Internalization Mediated By Recombinant Vaultssupporting

confidence: 88%

Section: Introductionmentioning

confidence: 99%

All-in-one biofabrication and loading of recombinant vaults in human cells

et al. 2022

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“…As noted above, inhibiting CSF1R or Periostin inhibits recruitment of both MGs and Macs, as does blocking chemokine receptor CXCR4 [23,37]. Additional chemokine or cytokine-dependent approaches have shown potential value for targeting Macs, specifically [42][43][44][45]. Finally, in an alternative approach, circulating monocytes that are Mac precursors, rather than more traditional mo-DC, have been employed in a recent clinical trial with encouraging and safe results [46].…”

Section: Macrophage Re-polarization and Re-direction In Gbmmentioning

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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“…For example, research has been conducted on DCs overexpressing the chemokine ligand 21 (CCL21) which function is to attract DCs and T cells. CCL21 has been used in a recent study as a CCL21-coupled vault nanoparticle using intratumoral injection and has been shown to decrease tumor volume in an in vivo model of glioma [48]. In case of transfection of DC's, an adenoviral vector expressing secondary lymphoid tissue chemokine (CCL21/SLC) was used.…”

Section: Immune Cellsmentioning

confidence: 99%