Metronomic Doses of Temozolomide Enhance the Efficacy of Carbon Nanotube CpG Immunotherapy in an Invasive Glioma Model

PloS One
Mao OuyangBehnam Badie

Abstract

Even when treated with aggressive current therapies, most patients with glioblastoma survive less than two years. Rapid tumor growth, an invasive nature, and the blood-brain barrier, which limits the penetration of large molecules into the brain, all contribute to the poor tumor response associated with conventional therapies. Immunotherapy has emerged as a therapeutic approach that may overcome these challenges. We recently reported that single-walled carbon nanotubes (SWCNTs) can be used to dramatically increase the immunotherapeutic efficacy of CpG oligonucleotides in a mouse model of glioma. Following implantation in the mouse brain, the tumor cell line used in these previous studies (GL261) tends to form a spherical tumor with limited invasion into healthy brain. In order to evaluate SWCNT/CpG therapy under more clinically-relevant conditions, here we report the treatment of a more invasive mouse glioma model (K-Luc) that better recapitulates human disease. In addition, a CpG sequence previously tested in humans was used to formulate the SWCNT/CpG which was combined with temozolomide, the standard of care chemotherapy for glioblastoma patients. We found that, following two intracranial administrations, SWCNT/CpG is well-to...Continue Reading

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Citations

Feb 13, 2017·Cancer Letters·Yu-Li ChenWen-Fang Cheng
May 28, 2020·Journal for Immunotherapy of Cancer·Dipongkor SahaRobert L Martuza
Jan 9, 2020·Cancer Cell International·Fangkun LiuZhixiong Liu
May 8, 2018·Neuro-oncology·Aida KarachiMaryam Rahman
Feb 6, 2019·Frontiers in Immunology·Thiago A PatenteJosé A M Barbuto
Sep 29, 2020·Frontiers in Cell and Developmental Biology·Zeyu WangQuan Cheng
Nov 1, 2017·Human Vaccines & Immunotherapeutics·Ziren KongWenbin Ma
Sep 24, 2019·Future Medicinal Chemistry·Raul OrtizJose Prados
Nov 13, 2020·Frontiers in Immunology·Joshua R D PearsonStephanie E B McArdle
Jan 9, 2019·Trends in Cancer·Luiz Henrique Medeiros GeraldoFlavia Regina Souza Lima
Mar 13, 2018·Bioconjugate Chemistry·Darya AlizadehJacob M Berlin

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Methods Mentioned

BETA
PCR
density gradient centrifugation
flow cytometry

Software Mentioned

prism
Voloom
FlowJo
Zeiss LSM Image Browser

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