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Treatment of rapidly growing K-BALB and CT26 mouse tumours using Semliki Forest virus and its derived vector
J W P Smyth1, M N Fleeton, B J Sheahan
1Department of Microbiology, Moyne Institute, Trinity College, Dublin 2, Ireland.
Abstract:
To assess the potential of immune stimulation in combination with apoptosis induction by Semliki Forest virus (SFV) and its derived vector for tumour treatment, we have utilized the poorly immunogenic and rapidly growing K-BALB and CT26 murine tumour models. Both cell lines underwent apoptosis and expressed viral antigen when infected with the SFV4 strain of SFV, or recombinant SFV (rSFV) virus-like particles (VLPs) encoding the p62-6k viral structural proteins. VLPs were used to immunize groups of BALB/c and BALB/c nu/nu mice prior to subcutaneous tumour induction and treatment. Direct intratumoral injection of VLPs or SFV4 resulted in an immediate and intense inflammatory reaction in immunized groups that was not observed in naive groups until day 5 of treatment, and was not observed in nu/nu groups. A significantly higher level of tumour growth inhibition was observed in immunocompetent groups than in athymic mice. For K-BALB tumours, SFV4 treated groups showed greater inhibition than that observed in VLP-treated groups, with immunization prior to treatment enhancing the overall antitumour effect and immune response. No significant difference was observed in CT26 tumours between VLP and SFV4-treated groups, but prior immunization considerably enhanced the antitumoural response. It is concluded that use of the inherent apoptosis-inducing capability of SFV or its vector, by perfusion in combination with immune stimulation, may have potential for the treatment of rapidly growing tumours.
Insights
Semliki Forest virus (SFV) and its vectors induce apoptosis and immune stimulation for potential cancer treatment. This approach showed significant tumor growth inhibition in immunocompetent mice, highlighting its therapeutic promise.
Area of Science:
- Oncology
- Virology
- Immunology
Background:
- Semliki Forest virus (SFV) exhibits apoptosis-inducing properties.
- Viral vectors derived from SFV can express viral antigens.
- Tumor treatment strategies often combine direct cell killing with immune system activation.
Purpose of the Study:
- To evaluate the potential of SFV and its derived vectors for tumor treatment.
- To assess the combined effects of immune stimulation and apoptosis induction.
- To investigate the efficacy in poorly immunogenic and rapidly growing murine tumor models.
Main Methods:
- Utilized K-BALB and CT26 murine tumor models.
- Infected tumor cells with SFV4 or recombinant SFV (rSFV) virus-like particles (VLPs).
- Administered VLPs or SFV4 via direct intratumoral injection in immunized and naive immunocompetent and athymic mice.
Main Results:
- SFV4 and rSFV VLPs induced apoptosis and viral antigen expression in tumor cells.
- Intratumoral injection led to intense inflammatory reactions in immunized groups.
- Significantly greater tumor growth inhibition was observed in immunocompetent mice compared to athymic mice.
- Prior immunization enhanced the anti-tumor effect and immune response, particularly for K-BALB tumors.
Conclusions:
- SFV and its vectors possess inherent apoptosis-inducing capabilities.
- Combining SFV-mediated apoptosis with immune stimulation shows potential for treating rapidly growing tumors.
- Further research into SFV-based therapies for cancer is warranted.
