Treatment of rapidly growing K-BALB and CT26 mouse tumours using Semliki Forest virus and its derived vector

Smyth, J. D.; Fleeton, Marina N.; Sheahan, B. J.; Atkins, Gregory J.

doi:10.1038/sj.gt.3302390

Cited by 35 publications

(30 citation statements)

References 36 publications

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“…In summary, rather than undergoing cell death consistent with apoptosis, we observed that the majority of cells were dying by other mechanisms. Corroborating these findings, Smyth et al (37) detected activated caspase in only a fraction of SFV-infected cancer cells throughout the course of infection. In addition, during infection with conditionally replicating adenovirus, cancer cells have been reported to die by mechanisms resembling necrosis, independent of major apoptotic pathways (38).…”

Section: Discussionmentioning

confidence: 79%

Oncolytic Capacity of Attenuated Replicative Semliki Forest Virus in Human Melanoma Xenografts in Severe Combined Immunodeficient Mice

et al. 2006

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Section: Discussionmentioning

confidence: 79%

Oncolytic Capacity of Attenuated Replicative Semliki Forest Virus in Human Melanoma Xenografts in Severe Combined Immunodeficient Mice

et al. 2006

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“…[6][7][8][9] Alphaviral vectors have recently been tested also in cancer targeting, and some of the results are extremely promising. For example, SFV 10,11 and Sindbis virus [12][13][14] vectors have been shown to be highly effective against both xenografts and orthotopic tumors in mice. These results have encouraged us to study the oncolytic potential of a replicative SFV virus strain or a replication-competent SFV vector in relevant tumor models.…”

mentioning

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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“…Alphavirus-based vectors have emerged as a promising tool for cancer gene therapy, as they combine an extraordinarily high expression level with the capacity to induce apoptosis in infected cells. 22 Thus, alphavirus vectors expressing reporter genes 23,24 or viral structural proteins 25 can mediate antitumor responses. In these models, the expression of low levels of type I IFN synergizes with the induction of apoptosis in tumor cells to trigger the immune response.…”

Section: Introductionmentioning

confidence: 99%

A Semliki Forest virus vector engineered to express IFNα induces efficient elimination of established tumors

et al. 2011

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Semliki Forest virus (SFV) represents a promising gene therapy vector for tumor treatment, because it produces high levels of recombinant therapeutic proteins while inducing apoptosis in infected cells. In this study, we constructed a SFV vector expressing murine interferon alpha (IFNa). IFNa displays antitumor activity mainly by enhancing an antitumor immune response, as well as by a direct antiproliferative effect. In spite of the antiviral activity of IFNa, SFV-IFN could be produced in BHK cells at high titers. This vector was able to infect TC-1 cells, a tumor cell line expressing E6 and E7 proteins of human papillomavirus, leading to high production of IFNa both in vitro and in vivo. When injected into subcutaneous TC-1 tumors implanted in mice, SFV-IFN was able to induce an E7-specific cytotoxic T lymphocyte response, and to modify tumor infiltrating immune cells, reducing the percentage of T regulatory cells and activating myeloid cells. As a consequence, SFV-IFN was able to eradicate 58% of established tumors treated 21 days after implantation with long-term tumor-free survival and very low toxicity. SFV-IFN was also able to induce significant antitumor responses in a subcutaneous tumor model of murine colon adenocarcimoma. These data suggest that local production of IFNa by intratumoral injection of recombinant SFV-IFN could represent a potent new strategy to treat tumors in patients.

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Treatment of rapidly growing K-BALB and CT26 mouse tumours using Semliki Forest virus and its derived vector

Cited by 35 publications

References 36 publications

Oncolytic Capacity of Attenuated Replicative Semliki Forest Virus in Human Melanoma Xenografts in Severe Combined Immunodeficient Mice

Oncolytic Capacity of Attenuated Replicative Semliki Forest Virus in Human Melanoma Xenografts in Severe Combined Immunodeficient Mice

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

A Semliki Forest virus vector engineered to express IFNα induces efficient elimination of established tumors

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