Immunohistochemical Characterization and Sensitivity to Human Adenovirus Serotypes 3, 5, and 11p of New Cell Lines Derived from Human Diffuse Grade II to IV Gliomas

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Niittykoski , M , zu Fraunberg , M V U , Martikainen , M , Rauramaa , T , Immonen , A , Koponen , S , Leinonen , V , Vaha-Koskela , M , Zhang , Q , Kuhnel , F , Mei , Y-F , Yla-Herttuala , S , Jaaskelainen , J E & Hinkkanen , A 2017 , ' Immunohistochemical Characterization and Sensitivity to Human Adenovirus Serotypes 3, 5, and 11p of New Cell Lines Derived from Human Diffuse Grade II to IV Gliomas ' , Translational oncology , vol. 10 , no. 5 , pp. 772-779 . https://doi.org/10.1016/j.tranon.2017.07.002

Title: Immunohistochemical Characterization and Sensitivity to Human Adenovirus Serotypes 3, 5, and 11p of New Cell Lines Derived from Human Diffuse Grade II to IV Gliomas
Author: Niittykoski, Minna; zu Fraunberg, Mikael von und; Martikainen, Miika; Rauramaa, Tuomas; Immonen, Arto; Koponen, Susanna; Leinonen, Ville; Vaha-Koskela, Markus; Zhang, Qiwei; Kuhnel, Florian; Mei, Ya-Fang; Yla-Herttuala, Seppo; Jaaskelainen, Juha E.; Hinkkanen, Ari
Contributor: University of Helsinki, Institute for Molecular Medicine Finland
Date: 2017-10
Language: eng
Number of pages: 8
Belongs to series: Translational oncology
ISSN: 1936-5233
URI: http://hdl.handle.net/10138/225103
Abstract: BACKGROUND: Oncolytic adenoviruses show promise in targeting gliomas because they do not replicate in normal brain cells. However, clinical responses occur only in a subset of patients. One explanation could be the heterogenic expression level of virus receptors. Another contributing factor could be variable activity of tumor antiviral defenses in different glioma subtypes. METHODS: We established a collection of primary low-passage cell lines from different glioma subtypes (3 glioblastomas, 3 oligoastrocytomas, and 2 oligodendrogliomas) and assessed them for receptor expression and sensitivity to human adenovirus (HAd) serotypes 3, 5, and 11p. To gauge the impact of antiviral defenses, we also compared the infectivity of the oncolytic adenoviruses in interferon (IFN)-pretreated cells with IFN-sensitive Semliki Forest virus (SFV). RESULTS: Immunostaining revealed generally low expression of HAd5 receptor CAR in both primary tumors and derived cell lines. HAd11p receptor CD46 levels were maintained at moderate levels in both primary tumor samples and derived cell lines. HAd3 receptor DSG-2 was reduced in the cell lines compared to the tumors. Yet, at equal multiplicities of infection, the oncolytic potency of HAd5 in vitro in tumor-derived cells was comparable to HAd11p, whereas HAd3 lysed fewer cells than either of the other two HAd serotypes in 72 hours. IFN blocked replication of SFV, while HAds were rather unaffected. CONCLUSIONS: Adenovirus receptor levels on glioma-derived cell lines did not correlate with infection efficacy and may not be a relevant indicator of clinical oncolytic potency. Adenovirus receptor analysis should be preferentially performed on biopsies obtained perioperatively.
Subject: SEMLIKI-FOREST-VIRUS
PRIMARY BRAIN-TUMORS
MALIGNANT GLIOMA
ONCOLYTIC ADENOVIRUS
GENE-THERAPY
REPLICATING ADENOVIRUS
GLIOBLASTOMA CELLS
STEM-CELL
IN-VIVO
EXPRESSION
3122 Cancers
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