1. Recombinant SLAMblind Measles Virus Is a Promising Candidate for Nectin-4-Positive Triple Negative Breast Cancer Therapy
- Author
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Tomoko Fujiyuki, Hiroki Sato, Mutsumi Awano, Misako Yoneda, Yosuke Amagai, Akihiro Sugai, Koichiro Shoji, Shosaku Hattori, Takeshi Kuraishi, and Chieko Kai
- Subjects
0301 basic medicine ,safety ,Cancer Research ,non-human primate ,lcsh:RC254-282 ,Virus ,Metastasis ,Measles virus ,03 medical and health sciences ,0302 clinical medicine ,Breast cancer ,medicine ,Pharmacology (medical) ,skin and connective tissue diseases ,Triple-negative breast cancer ,oncolytic virus ,oncovirotherapy ,biology ,business.industry ,systemic ,lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,biology.organism_classification ,medicine.disease ,Metastatic breast cancer ,Oncolytic virus ,030104 developmental biology ,Oncology ,Cell culture ,030220 oncology & carcinogenesis ,measles virus ,triple negative breast cancer ,nectin-4 ,intravenous ,Cancer research ,Molecular Medicine ,Original Article ,business - 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., Graphical Abstract, Triple negative breast cancer (TNBC) is one of the most refractory breast cancer types. A recombinant measles virus, rMV-SLAMblind, infected nectin-4-positive TNBC cells and significantly suppressed the tumor growth in xenograft models. Thus, rMV-SLAMblind is a promising candidate as a therapeutic agent for TNBC.
- Published
- 2020