Related Experiment Video
Updated: Jul 12, 2026
Paramyxoviruses for Tumor-targeted Immunomodulation: Design and Evaluation Ex Vivo
Published on: January 7, 2019
An immunocompetent murine model for oncolysis with an armed and targeted measles virus
Guy Ungerechts1, Christoph Springfeld, Marie E Frenzke
1Molecular Medicine Program and Virology and Gene Therapy Track, Mayo Clinic College of Medicine, Rochester, Minnesota 55902, USA.
Abstract:
An immunocompetent model is required to test therapeutic regimens for clinical trials with the oncolytic measles virus (MV). Toward developing this model, a retargeted MV that enters murine colon adenocarcinoma cells forming tumors in syngeneic C57BL/6 mice was generated. Since MV infection tends to be less efficient in murine than in human cells, the targeted virus was also armed with the prodrug convertase, purine nucleoside phosphorylase (PNP), and named MV-PNP-antiCEA. We have shown before that in cultured cells, infection with this virus activated the prodrug, 6-methylpurine-2'-deoxyriboside (MeP-dR), causing extensive cytotoxicity. When injected intratumorally (IT), MV-PNP-antiCEA inhibited subcutaneous tumor growth marginally, but subsequent administration of the prodrug enhanced the oncolytic effect. Systemic delivery of MV-PNP-antiCEA alone had no substantial oncolytic effects, but in combination with the prodrug it was therapeutic, revealing synergistic effects between virus and prodrug. Immunosuppression with cyclophosphamide (CPA) retarded the appearance of MV neutralizing antibodies and enhanced oncolytic efficacy: survival was 100%, with 9 out of 10 animals going into complete remission. This immunocompetent murine model facilitates the testing of therapeutic regimens for clinical trials.
Insights
Researchers developed a novel oncolytic measles virus (MV-PNP-antiCEA) for immunocompetent mouse models. Combining this virus with a prodrug demonstrated significant therapeutic synergy, leading to complete tumor remission in most subjects.
Area of Science:
- Oncolytic virotherapy
- Cancer immunotherapy
- Murine models
Background:
- Oncolytic measles virus (MV) requires immunocompetent models for clinical trial testing.
- Murine cells show less susceptibility to MV infection compared to human cells.
Purpose of the Study:
- To develop a retargeted MV (MV-PNP-antiCEA) for murine colon adenocarcinoma.
- To evaluate the therapeutic efficacy of MV-PNP-antiCEA combined with a prodrug (MeP-dR) in immunocompetent mice.
Main Methods:
- Generation of a retargeted MV armed with purine nucleoside phosphorylase (PNP).
- Intratumoral and systemic administration of MV-PNP-antiCEA and the prodrug MeP-dR.
- Evaluation of tumor growth inhibition, therapeutic effects, and survival rates.
- Assessment of immunosuppression using cyclophosphamide (CPA).
Main Results:
- Intratumoral MV-PNP-antiCEA showed marginal tumor growth inhibition, enhanced by prodrug administration.
- Systemic delivery of MV-PNP-antiCEA combined with the prodrug was therapeutic, showing synergistic effects.
- Immunosuppression with CPA improved oncolytic efficacy, resulting in 100% survival and 90% complete remission.
Conclusions:
- MV-PNP-antiCEA combined with a prodrug is a promising therapeutic strategy.
- An immunocompetent murine model was successfully established for testing oncolytic virotherapy regimens.
- This model facilitates the preclinical testing of therapeutic strategies for clinical trials.
