Type I interferon response against viral and non‐viral gene transfer in human tumor and primary cell lines

Rautsi, Outi; Lehmusvaara, Saara; Salonen, Tuula; Häkkinen, Katja; Sillanpää, Maarit; Hakkarainen, Tanja; Heikkinen, Sami; Vähäkangas, Elisa; Ylä‐Herttuala, Seppo; Hinkkanen, Ari; Julkunen, Ilkka; Wahlfors, Jarmo; Pellinen, Riikka

doi:10.1002/jgm.997

Cited by 17 publications

(25 citation statements)

References 40 publications

(44 reference statements)

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“…20,21 Once activated, innate receptors regulate type I interferon (IFN) and nuclear factor-kB-dependent gene expression, or process cytokines such as pro-interleukin (IL)-1b to their active and secreted forms. AAV vectors do not appear to engage pattern recognition receptors such as toll-like receptors, 22 fail to induce type I IFN responses 23 and do not induce IL-1b processing (Zaiss and Muruve, unpublished observations).…”

Section: Innate Immunitymentioning

confidence: 99%

Immunity to adeno-associated virus vectors in animals and humans: a continued challenge

2008

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Section: Innate Immunitymentioning

confidence: 99%

Immunity to adeno-associated virus vectors in animals and humans: a continued challenge

2008

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“…Protein concentration was measured with the Bradford method at A 595 . Western blotting against MxA protein was performed as described earlier by Rautsi et al, 20 using rabbit anti-MxA antibody (1:2,000 dilution, kindly provided by Professor Ilkka Julkunen, National Public Health Institute, Helsinki, Finland) and HRP-conjugated anti-rabbit IgG antibody (1:200,000 dilution, Amersham Biosciences, Little Chalfont, UK).…”

Section: Western Blottingmentioning

confidence: 99%

Evaluation of cancer virotherapy with attenuated replicative Semliki forest virus in different rodent tumor models

Määttä

Liimatainen

Wahlfors

et al. 2007

Intl Journal of Cancer

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Semliki Forest virus (SFV) is one of the latest candidates for a virotherapeutic agent against cancer, and recent studies have demonstrated its efficacy in tumor models. In the present study, we examined the antitumor efficacy of an avirulent SFV strain A7(74) and its derivative, a replication-competent SFV vector VA7-EGFP, in a partially immunodeficient mouse tumor model (subcutaneous A549 human lung adenocarcinoma in NMRI nu/nu mouse) and in an immunocompetent rat tumor model (intracranial BT4C glioma in BDIX rat). When subcutaneous mouse tumors were injected 3 times with VA7-EGFP, intratumorally treated animals showed almost complete inhibition of tumor growth, while systemically treated mice displayed only delayed tumor growth (intravenous injection) or no response at all (intraperitoneal injection). This was at least partially due to a strong type I interferon (IFN) response in the tumors. The animals did not display any signs of abnormal behavior or encephalitis, even though SFV-positive foci were detected in the brain after the initial blood viremia. Intracranial rat tumors were injected directly with SFV A7(74) virus and monitored with magnetic resonance imaging. Tumor growth was significantly reduced (p < 0.05) with one virus injection, but the tumor size continued to increase after a lag period and none of the treated animals survived. Three virus injections or T-cell suppression with dexamethasone did not significantly improve treatment efficacy. It appeared that the local virotherapy induced extensive production of neutralizing anti-SFV antibodies that most likely contributed to the insufficient treatment efficacy. In conclusion, we show here that SFV A7(74) is a potential oncolytic agent for cancer virotherapy, but major immunological hurdles may need to be overcome before the virus can be clinically tested. ' 2007 Wiley-Liss, Inc.

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“…One characteristic of Saos2LM7 cells that makes them remarkably sensitive for oncolytic SFV could be their defective innate immune response. We studied here the MxA response to infection with VA7-EGFP in Saos2LM7 cells with a method previously described by Rautsi and colleagues (40). No accumulation of MxA was observed (data not shown).…”

Section: Discussionmentioning

confidence: 95%

“…7 This hypothesis is supported by the fact that similar pattern of rapid emergence of resistant cell population was observed in A549 lung carcinoma cells infected with the VA7-EGFP (39). A549 cells display a robust type I IFN response and strong MxA expression against SFV infection (40). The type I IFN response and the MxA protein itself have been found to inhibit SFV infection both in vitro and in vivo (41,(42)(43)(44)(45).…”

Section: Discussionmentioning

confidence: 99%

Oncolytic Semliki Forest Virus Vector as a Novel Candidate against Unresectable Osteosarcoma

et al. 2008

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Oncolytic viruses are a promising tool for treatment of cancer. We studied an oncolytic Semliki Forest virus (SFV) vector, VA7, carrying the enhanced green fluorescent protein gene (EGFP), as a novel virotherapy candidate against unresectable osteosarcoma. The efficiency and characteristics of the VA7-EGFP treatment were compared with a widely studied oncolytic adenovirus, Ad5#24, both in vitro and in vivo. VA7-EGFP resulted in more rapid oncolysis and was more efficient at low multiplicities of infection (MOI) when compared with Ad5#24 in vitro. Yet, in MG-63 cells, a subpopulation resistant to the VA7-EGFP vector emerged. In subcutaneous human osteosarcoma xenografts in nude mice treatment with either vector reduced tumor size, whereas tumors in control mice expanded quickly. The VA7-EGFP-treated tumors were either completely abolished or regressed to pinpoint size. The efficacy of VA7-EGFP vector was studied also in an orthotopic osteosarcoma nude mouse model characterized by highly aggressive tumor growth. Treatment with oncolytic SFV extended survival of the animals significantly (P < 0.01), yet none of the animals were finally cured. Sera from SFV-treated mice contained neutralizing antibodies, and as nude mice are not able to establish IgG response, the result points out the role of IgM class antibodies in clearance of virus from peripheral tumors. Furthermore, biodistribution analysis at the survival end point verified the presence of virus in some of the brain samples, which is in line with previous studies demonstrating that IgG is required for clearance of SFV from central nervous system.

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Type I interferon response against viral and non‐viral gene transfer in human tumor and primary cell lines

Cited by 17 publications

References 40 publications

Immunity to adeno-associated virus vectors in animals and humans: a continued challenge

Immunity to adeno-associated virus vectors in animals and humans: a continued challenge

Evaluation of cancer virotherapy with attenuated replicative Semliki forest virus in different rodent tumor models

Oncolytic Semliki Forest Virus Vector as a Novel Candidate against Unresectable Osteosarcoma

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