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Paramyxoviruses for Tumor-targeted Immunomodulation: Design and Evaluation Ex Vivo
Published on: January 7, 2019
A measles virus selectively blind to signaling lymphocytic activation molecule shows anti-tumor activity against lung
Tomoko Fujiyuki1, Misako Yoneda1, Yosuke Amagai1
1Laboratory Animal Research Center, The Institute of Medical Science, The University of Tokyo, Shirokanedai, Minato-ku, Tokyo, 108-8639, Japan.
Abstract:
Lung cancer cells, particularly those of non-small-cell lung cancer, are known to express Nectin-4. We previously generated a recombinant measles virus that uses Nectin-4 as its receptor but cannot bind its original principal receptor, signaling lymphocyte activation molecule (SLAM). This virus (rMV-SLAMblind) infects and kills breast cancer cells in vitro and in a subcutaneous xenograft model. However, it has yet to be determined whether rMV-SLAMblind is effective against other cancer types and in other tumor models that more closely represent disease. In this study, we analyzed the anti-tumor activity of this virus towards lung cancer cells using a modified variant that encodes green fluorescent protein (rMV-EGFP-SLAMblind). We found that rMV-EGFP-SLAMblind efficiently infected nine, human, lung cancer cell lines, and its infection resulted in reduced cell viability of six cell lines. Administration of the virus into subcutaneous tumors of xenotransplanted mice suppressed tumor growth. In addition, rMV-EGFP-SLAMblind could target scattered tumor masses grown in the lungs of xenotransplanted mice. These results suggest that rMV-SLAMblind is oncolytic for lung cancer and that it represents a promising tool for the treatment of this disease.
Insights
A modified measles virus, rMV-EGFP-SLAMblind, effectively targets and reduces lung cancer cell viability. This oncolytic virus shows promise for treating lung cancer by suppressing tumor growth in preclinical models.
Area of Science:
- Oncology
- Virology
- Gene Therapy
Background:
- Non-small cell lung cancer (NSCLC) cells express Nectin-4, a potential target for oncolytic viruses.
- A previously developed recombinant measles virus (rMV-SLAMblind) targets Nectin-4 and shows efficacy against breast cancer.
Purpose of the Study:
- To evaluate the anti-tumor activity of a modified measles virus (rMV-EGFP-SLAMblind) against lung cancer cells and in relevant preclinical models.
- To determine if rMV-EGFP-SLAMblind can infect and reduce the viability of human lung cancer cell lines.
- To assess the efficacy of rMV-EGFP-SLAMblind in suppressing tumor growth in vivo.
Main Methods:
- In vitro infection of nine human lung cancer cell lines with rMV-EGFP-SLAMblind.
- Assessment of cell viability following viral infection.
- In vivo studies using xenotransplanted mouse models with subcutaneous and disseminated lung tumors.
Main Results:
- rMV-EGFP-SLAMblind efficiently infected all nine tested lung cancer cell lines.
- Viral infection led to reduced cell viability in six of the cell lines.
- The virus suppressed subcutaneous tumor growth and targeted scattered lung tumor masses in mice.
Conclusions:
- The Nectin-4-targeting measles virus, rMV-EGFP-SLAMblind, demonstrates oncolytic activity against lung cancer.
- This modified measles virus is a promising candidate for the development of novel lung cancer therapies.
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