Recombinant SLAMblind Measles Virus Is a Promising Candidate for Nectin-4-Positive Triple Negative Breast Cancer Therapy

• Published in: Molecular therapy. Oncolytics 2020-12, Vol.19, p.127-135
• Main Authors: Fujiyuki, Tomoko, Amagai, Yosuke, Shoji, Koichiro, Kuraishi, Takeshi, Sugai, Akihiro, Awano, Mutsumi, Sato, Hiroki, Hattori, Shosaku, Yoneda, Misako, Kai, Chieko
• Format: Article
• Language: English
• Subjects: intravenous; measles virus; nectin-4; non-human primate; oncolytic virus; oncovirotherapy; Original; safety; systemic; triple negative breast cancer
• ISSN: 2372-7705; 2372-7705
• DOI: 10.1016/j.omto.2020.09.007

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. [Display omitted] 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.