Sökning: WFRF:(Ramachandran Mohanraj)
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Safe and effective ...
Safe and effective treatment of experimental neuroblastoma and glioblastoma using systemically administered triple microRNA-detargeted oncolytic Semliki Forest virus
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- Ramachandran, Mohanraj, 1988- (författare)
- Uppsala universitet,Science for Life Laboratory, SciLifeLab,Klinisk immunologi,Magnus Essand
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- Yu, Di, 1985- (författare)
- Uppsala universitet,Science for Life Laboratory, SciLifeLab,Klinisk immunologi
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- Dyczynski, Matheus (författare)
- Uppsala universitet,Klinisk immunologi,Science for Life Laboratory, SciLifeLab,Karolinska Inst, Dept Pathol & Oncol, CCK, Stockholm, Sweden.
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- Baskaran, Sathishkumar (författare)
- Uppsala universitet,Neuroonkologi,Science for Life Laboratory, SciLifeLab
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- Zhang, Lei (författare)
- Uppsala universitet,Vaskulärbiologi,Science for Life Laboratory, SciLifeLab
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- Lulla, Aleksei (författare)
- Institute of Technology, University of Tartu, Estonia.
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- Lulla, Valeria (författare)
- Institute of Technology, University of Tartu, Estonia.
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- Saul, Sirle (författare)
- Institute of Technology, University of Tartu, Estonia.
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- Nelander, Sven (författare)
- Uppsala universitet,Neuroonkologi,Science for Life Laboratory, SciLifeLab
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- Dimberg, Anna (författare)
- Uppsala universitet,Vaskulärbiologi,Science for Life Laboratory, SciLifeLab
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- Merits, Andres (författare)
- Institute of Technology, University of Tartu, Estonia.
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- Leja-Jarblad, Justyna, 1982- (författare)
- Uppsala universitet,Klinisk immunologi,Science for Life Laboratory, SciLifeLab
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- Essand, Magnus (författare)
- Uppsala universitet,Science for Life Laboratory, SciLifeLab,Klinisk immunologi
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(creator_code:org_t)
- American Association for Cancer Research, 2017
- 2017
- Engelska.
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Ingår i: Clinical Cancer Research. - : American Association for Cancer Research. - 1078-0432 .- 1557-3265. ; 23:6, s. 1519-1530
- Relaterad länk:
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https://urn.kb.se/re...
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https://doi.org/10.1...
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Abstract
Ämnesord
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- PURPOSE:Glioblastoma multiforme (GBM) and high-risk neuroblastoma are cancers with poor outcome. Immunotherapy in the form of neurotropic oncolytic viruses is a promising therapeutic strategy for these malignancies. Here we evaluate the oncolytic potential of the neurovirulent and partly interferon (IFN)-β-resistant Semliki Forest virus (SFV)-4 in GBMs and neuroblastomas. To reduce neurovirulence we constructed SFV4miRT, which is attenuated in normal CNS cells through insertion of microRNA target sequences for miR124, miR125, miR134 Experimental Design:Oncolytic activity of SFV4miRT was examined in mouse neuroblastoma and GBM cell lines and in patient-derived human glioblastoma cell cultures (HGCC). In vivo neurovirulence and therapeutic efficacy was evaluated in two syngeneic orthotopic glioma models (CT-2A, GL261) and syngeneic subcutaneous neuroblastoma model (NXS2). The role of IFN-β in inhibiting therapeutic efficacy was investigated.RESULTS:The introduction of microRNA target sequences reduced neurovirulence of SFV4 in terms of attenuated replication in mouse CNS cells and ability to cause encephalitis when administered intravenously. A single intravenous injection of SFV4miRT prolonged survival and cured 4 of 8 mice (50%) with NXS2 and 3 of 11 mice (27%) with CT-2A, but not for GL261 tumor bearing mice. In vivo therapeutic efficacy in different tumor models inversely correlated to secretion of IFN-β by respective cells upon SFV4 infection in vitro Similarly, killing efficacy of HGCC lines inversely correlated to IFN-β response and interferon-α⁄β receptor (IFNAR)-1 expression.CONCLUSIONS:SFV4miRT has reduced neurovirulence, while retaining its oncolytic potential. SFV4miRT is an excellent candidate for treatment of GBMs and neuroblastomas with low IFN-β secretion.
Ämnesord
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Andra medicinska och farmaceutiska grundvetenskaper (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Other Basic Medicine (hsv//eng)
Nyckelord
- Semliki Forest virus
- Glioblastoma
- Neuroblastoma
- Oncolytic virus immunotherapy
- Type-I antiviral response
- Oncology
- Onkologi
- Biology with specialization in Molecular Biotechnology
- Biologi med inriktning mot molekylär bioteknik
Publikations- och innehållstyp
- ref (ämneskategori)
- art (ämneskategori)
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Ramachandran, Mo ...
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Yu, Di, 1985-
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Dyczynski, Mathe ...
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Baskaran, Sathis ...
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Zhang, Lei
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Lulla, Aleksei
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Lulla, Valeria
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Saul, Sirle
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Nelander, Sven
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Dimberg, Anna
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Merits, Andres
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Leja-Jarblad, Ju ...
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Essand, Magnus
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Uppsala universitet