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Updated: Dec 2, 2025
Paramyxoviruses for Tumor-targeted Immunomodulation: Design and Evaluation Ex Vivo
Published on: January 7, 2019
Recombinant SLAMblind Measles Virus Is a Promising Candidate for Nectin-4-Positive Triple Negative Breast Cancer
Tomoko Fujiyuki1, Yosuke Amagai1, Koichiro Shoji1
1Laboratory Animal Research Center, The Institute of Medical Science, The University of Tokyo, 4-6-1 Shirokanedai, Minato-ku, Tokyo 108-8639, Japan.
Abstract:
One of the most refractory breast cancer types is triple negative (TN) breast cancer, in which cells are resistant to both hormone and Herceptin treatments and, thus, often cause recurrence and metastasis. Effective treatments are needed to treat TN breast cancer. We previously demonstrated that rMV-SLAMblind, a recombinant measles virus, showed anti-tumor activity against breast cancer cells. Here, we examined whether rMV-SLAMblind is effective for treating TN breast cancer. Nectin-4, a receptor for rMV-SLAMblind, was expressed on the surface of 75% of the analyzed TN breast cancer cell lines. rMV-SLAMblind infected the nectin-4-expressing TN breast cancer cell lines, and significantly decreased the viability in half of the analyzed cell lines in vitro. Additionally, intratumoral injection of rMV-SLAMblind suppressed tumor growth in xenografts of MDA-MB-468 and HCC70 cells. To assess treatment for metastatic breast cancer, we performed intravenous administration of the luciferase-expressing-rMV-SLAMblind to MDA xenografted mice. Virus replicated in the tumor and resulted in significant suppression of the tumor growth. The safety of the virus was tested by its intravenous injection into healthy cynomolgus monkeys, which did not cause any measles-like symptoms. These results suggest that rMV-SLAMblind is a promising candidate as a therapeutic agent for treating metastatic and/or TN type breast cancer.
Insights
Recombinant measles virus rMV-SLAMblind shows promise for treating triple-negative breast cancer. This virus effectively reduced tumor growth in preclinical models and demonstrated safety in non-human primates.
Area of Science:
- Oncolytic virology
- Cancer therapeutics
Background:
- Triple-negative breast cancer (TNBC) is aggressive and lacks effective treatments.
- Recombinant measles virus (rMV-SLAMblind) has shown prior anti-tumor activity.
Purpose of the Study:
- To evaluate the efficacy of rMV-SLAMblind against TNBC.
- To assess its potential as a therapeutic agent for metastatic breast cancer.
Main Methods:
- Assessed Nectin-4 receptor expression on TNBC cell lines.
- Tested rMV-SLAMblind's in vitro efficacy and in vivo tumor suppression in xenograft models.
- Evaluated safety in cynomolgus monkeys.
Main Results:
- Nectin-4 was expressed on 75% of TNBC cell lines.
- rMV-SLAMblind reduced TNBC cell viability in vitro and suppressed tumor growth in vivo.
- Intravenous administration of rMV-SLAMblind inhibited tumor growth in metastatic models.
- The virus was safe in non-human primates, showing no measles-like symptoms.
Conclusions:
- rMV-SLAMblind demonstrates significant anti-tumor activity against TNBC.
- The virus is a promising therapeutic candidate for metastatic and TNBC.
- Further clinical investigation is warranted.
