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

Tomoko Fujiyuki; Yosuke Amagai; Koichiro Shoji; Takeshi Kuraishi; Akihiro Sugai; Mutsumi Awano; Hiroki Sato; Shosaku Hattori; Misako Yoneda; Chieko Kai

doi:10.1016/j.omto.2020.09.007

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

Mol Ther Oncolytics. 2020 Sep 30:19:127-135. doi: 10.1016/j.omto.2020.09.007. eCollection 2020 Dec 16.

Authors

Affiliations

¹ Laboratory Animal Research Center, The Institute of Medical Science, The University of Tokyo, 4-6-1 Shirokanedai, Minato-ku, Tokyo 108-8639, Japan.
² Amami Laboratory of Injurious Animals, The Institute of Medical Science, The University of Tokyo, 802 Tean-Sude, Setouchisho, Oshima-gun, Kagoshima 894-1531, 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.

Keywords: intravenous; measles virus; nectin-4; non-human primate; oncolytic virus; oncovirotherapy; safety; systemic; triple negative breast cancer.