Glioma Virotherapy: Effects of Innate Immune Suppression and Increased Viral Replication Capacity

Friedman, Avner; Tian, Jianjun Paul; Fulci, Giulia; Chiocca, E. Antonio; Wang, Jin

doi:10.1158/0008-5472.can-05-2661

Cited by 189 publications

(158 citation statements)

References 20 publications

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“…Mathematical modeling shows that the balance between the rate of tumor-cell growth and virus spread is a critical determinant of the outcome of oncolytic virus infection. 5 Whether chemotherapy acts directly on tumor cells by inducing cell arrest or cell death or indirectly by blocking tumor angiogenesis or inhibiting the host immunoresponse, the resulting delay in tumor growth may provide the oncolytic virus with a wider window of opportunity to overcome the challenge imposed by the growth kinetics of the tumor. Several preclinical studies have showed that RAD001 induces potent anti-cancer effect with negligible toxicity.…”

Section: Introductionmentioning

confidence: 99%

Combination of the oncolytic adenovirus ICOVIR-5 with chemotherapy provides enhanced anti-glioma effect in vivo

et al. 2007

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Novel therapies are clearly needed for gliomas, and the combination of oncolytic vectors with chemotherapy possesses a significant hope for the treatment of this malignancy. In addition, combination with chemotherapy allows for lower virus doses to achieve anticancer effect, thus resulting in lower undesirable toxicities due to viral proteins. In this work, we sought to determine whether combination of an oncolytic adenovirus ICOVIR-5, with RAD001 or temozolomide (TMZ) could result in enhanced anti-glioma effect in vivo. We assessed the in vitro cytotoxic effect and replication properties of ICOVIR-5 in combination with RAD001 or TMZ in U87 MG glioma cell line by MTT and TCID 50 , respectively. Our data showed that in vitro treatment with RAD001 or TMZ not only interfered with adenovirus replication but, in addition, enhanced its oncolytic properties. To evaluate the in vivo anticancer effect, athymic mice bearing glioma xenografts (5 Â 10 5 U87 MG cells/animal) received a single intratumoral injection of ICOVIR-5 (10 7 PFU/animal). RAD001 was given as a regimen of 5 mg/kg 5 days per week until the end of the experiment and TMZ was administered for 5 days at 7.5 mg/kg/mice. Of significance, combination of ICOVIR-5 with RAD001 or TMZ showed a potent antiglioma effect in vivo, resulting in a dramatic extension of the median animal survival and in 20-40% animals becoming free of disease beyond 90 days.

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Section: Introductionmentioning

confidence: 99%

Combination of the oncolytic adenovirus ICOVIR-5 with chemotherapy provides enhanced anti-glioma effect in vivo

et al. 2007

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“…While the low dilutions of measles virus caused higher cytotoxic inhibition rate. This result highlights the competition between viral replication, tumor cell growth and the death rate of infected tumor cells (21). Dingli et al (22) reported that the virus in high concentration cannot infect tumor cells because the surface receptors of tumor cells will be saturated with virus ligands.…”

Section: Discussionmentioning

confidence: 93%

Investigation of Live Attenuated Measles Virus Vaccine as Anti Tumor Agent

Ismaee

Al-Shammari²,

Salih

2017

JNUS

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This study was carried out to evaluate the antitumor effect of live attenuated measles virus Schwarz (MV) vaccine strain on tumor cell lines in vitro. Live attenuated measles virus Schwarz vaccine strain was obtained from Aventis Pasteur, France. Live attenuated measles virus Schwarz strain was propagated on Vero, human Rhabdomyosarcoma (RD) and human GlioblastomaMultiform (GBM) cell lines which were supplied by Iraqi Center for Cancer and Medical Genetic Researches (ICCMGR). Results revealed that cell fusion occurred after 24 h of infection. The infected confluent monolayer appeared to be covered with syncytia with granulation and vaculation of cells after 72 to 120 h. Moreover, the formation of large round empty plaque spaces was observed in infected cells. Results of oncolytic cytopathic effect showed that after 120 h of exposure alterations in morphology of Vero, RD and GBM cells. Cells were rounded, shrink, clustered cells and large empty space with cell debris as a result of cell lysis and death. Haemadsorption effect of MV was studied and result recorded that all cell lines infected with virus have the ability for haemadsorption human red blood cells after 72 h of infection. While uninfected cells gave negative results. Detection of MV H protein by monoclonal antibodies in infected cells of all cell lines by immunocytochemistry assay gave positive results (brown color) in cytoplasm of infected cells. Cell viability was measured after 72 h of infection by MTT assay. Results showed a significant cytotoxic effect for measles virus (P ≤0.05) on growth of RD and GBM cell lines at the first dilution and the second one after 72 h of infection. When the dilution increases, there was a significant decline in the inhibitory effect with a significant cytotoxic effect as compared with the control. Also, concentrated inoculums of measles virus showed a significant cytotoxic effect when compared with the control.

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“…It has been reported that cyclophosphamide enhances glioma virotherapy by inhibiting innate immune responses. 41,63 We observed that treatment of mice with cyclophosphamide before injection of trastuzumab-bound virus enhanced the luminescent signal in the tumors (Figure 7a.4), whereas in the absence of cyclophosphamide, luminescence was only seen in the spleen area (data not shown).…”

Section: Her-2 Targeting Of Prostate Cancermentioning

confidence: 88%

Lentiviruses with trastuzumab bound to their envelopes can target and kill prostate cancer cells

Moussavi

et al. 2009

Cancer Gene Ther

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In this study, we took advantage of the overexpression of human epidermal growth factor receptor 2 (HER-2) in prostate cancers to design lentiviruses with modified envelope proteins that bind antibodies to specific cell-surface antigens. When bound to trastuzumab (Herceptin, Genentech, CA), lentiviruses were able to selectively infect androgen-sensitive LNCaP and castrationresistant C4-2 human prostate cancer cell lines, both of which express high levels of HER-2. To test for a therapeutic effect, we engineered our antibody-binding lentiviruses to express thymidine kinase, which can convert the non-toxic pro-drug ganciclovir (GCV) into a cytotoxic form. LNCaP and C4-2 cells infected by these viruses were sensitive to GCV killing. In vivo, C4-2 xenograft tumors treated either intratumorally or i.v. with trastuzumab-bound lentivirus expressed luciferase, although the latter route was less tumor specific. When a prostate-specific promoter for governing luciferase expression was combined with trastuzumab-mediated delivery, there was a further enrichment in targeting viral gene expression in prostate tumors. In conclusion, we found that although prostate cancers that express high levels of HER-2 are resistant to the killing effects of trastuzumab, they can be targeted for selective gene expression and destruction by viruses with envelope proteins engineered to bind this antibody.

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Glioma Virotherapy: Effects of Innate Immune Suppression and Increased Viral Replication Capacity

Cited by 189 publications

References 20 publications

Combination of the oncolytic adenovirus ICOVIR-5 with chemotherapy provides enhanced anti-glioma effect in vivo

Combination of the oncolytic adenovirus ICOVIR-5 with chemotherapy provides enhanced anti-glioma effect in vivo

Investigation of Live Attenuated Measles Virus Vaccine as Anti Tumor Agent

Lentiviruses with trastuzumab bound to their envelopes can target and kill prostate cancer cells

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