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Updated: Jul 15, 2026
Paramyxoviruses for Tumor-targeted Immunomodulation: Design and Evaluation Ex Vivo
Published on: January 7, 2019
Evaluation of cancer virotherapy with attenuated replicative Semliki forest virus in different rodent tumor models
Ann-Marie Määttä1, Timo Liimatainen, Tiina Wahlfors
1Department of Biotechnology and Molecular Medicine, A. I. Virtanen Institute, University of Kuopio, Kuopio, Finland.
Abstract:
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.
Insights
Semliki Forest virus (SFV) shows potential as an oncolytic agent for cancer virotherapy. However, immunological responses, such as interferon and antibody production, hinder its clinical application.
Area of Science:
- Oncology
- Virology
- Immunology
Background:
- Semliki Forest virus (SFV) is being investigated as a potential virotherapeutic agent for cancer.
- Previous studies indicate SFV efficacy in preclinical tumor models.
Purpose of the Study:
- To evaluate the antitumor efficacy of an avirulent SFV strain (A7(74)) and a replication-competent SFV vector (VA7-EGFP).
- To assess efficacy in both a mouse xenograft model and an immunocompetent rat glioma model.
Main Methods:
- Intratumoral and systemic administration of VA7-EGFP in subcutaneous human lung adenocarcinoma mouse model.
- Direct injection of SFV A7(74) into intracranial rat gliomas, monitored by MRI.
- Evaluation of tumor growth inhibition, animal survival, and host immune responses (type I interferon, neutralizing antibodies).
Main Results:
- Intratumoral VA7-EGFP led to near-complete inhibition of subcutaneous mouse tumors.
- Systemic VA7-EGFP showed delayed tumor growth in mice, attributed partly to type I interferon response.
- SFV A7(74) injection in rats significantly reduced tumor growth but did not improve survival, with evidence of neutralizing antibody production.
Conclusions:
- SFV A7(74) demonstrates potential as an oncolytic virus for cancer therapy.
- Significant immunological hurdles, including interferon responses and neutralizing antibody production, must be addressed for clinical translation.
