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Journal of Neuro-Oncology
Published in: Journal of Neuro-Oncology 3/2020

01-05-2020 | Glioblastoma | Laboratory Investigation

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

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

Published in: Journal of Neuro-Oncology | Issue 3/2020

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Abstract

Purpose

Glioblastoma (GBM) is the most common and malignant primary adult brain tumor. Current care includes surgical resection, radiation, and chemotherapy. Recent clinical trials for GBM have demonstrated extended survival using interventions such as tumor vaccines or tumor-treating fields. However, prognosis generally remains poor, with expected survival of 20 months after randomization. Chemokine-based immunotherapy utilizing CCL21 locally recruits lymphocytes and dendritic cells to enhance host antitumor response. Here, we report a preliminary study utilizing CPZ-vault nanoparticles as a vehicle to package, protect, and steadily deliver therapy to optimize CCL21 therapy in a murine flank model of GBM.

Methods

GL261 cells were subcutaneously injected into the left flank of eight-week-old female C57BL/6 mice. Mice were treated with intratumoral injections of either: (1) CCL21-packaged vault nanoparticles (CPZ-CCL21), (2) free recombinant CCL21 chemokine empty vault nanoparticles, (3) empty vault nanoparticles, or 4) PBS.

Results

The results of this study showed that CCL21-packaged vault nanoparticle injections can decrease the tumor volume in vivo. Additionally, this study showed mice injected with CCL21-packaged vault nanoparticle had the smallest average tumor volume and remained the only treatment group with a negative percent change in tumor volume.

Conclusions

This preliminary study establishes vault nanoparticles as a feasible vehicle to increase drug delivery and immune response in a flank murine model of GBM. Future animal studies involving an intracranial orthotopic tumor model are required to fully evaluate the potential for CCL21-packaged vault nanoparticles as a strategy to bypass the blood brain barrier, enhance intracranial immune activity, and improve intracranial tumor control and survival.
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Metadata
Title
Intratumor injection of CCL21-coupled vault nanoparticles is associated with reduction in tumor volume in an in vivo model of glioma
Authors
Brittany L. Voth
Panayiotis E. Pelargos
Natalie E. Barnette
Nikhilesh S. Bhatt
Cheng Hao Jacky Chen
Carlito Lagman
Lawrance K. Chung
Thien Nguyen
John P. Sheppard
Prasanth Romiyo
Sergey Mareninov
Valerie A. Kickhoefer
William H. Yong
Leonard H. Rome
Isaac Yang
Publication date
01-05-2020
Publisher
Springer US
Published in
Journal of Neuro-Oncology / Issue 3/2020
Print ISSN: 0167-594X
Electronic ISSN: 1573-7373
DOI
https://doi.org/10.1007/s11060-020-03479-8

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