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Oncolytic Urabe mumps virus: A promising virotherapy for triple-negative breast cancer

Marshall D Behrens1, Robert J Stiles1, Gennett M Pike1,2

  • 1Department of Molecular Medicine, Mayo Clinic, 200 First Street, SW, Rochester, MN 55905, USA.

Molecular Therapy Oncolytics
|December 2, 2022
PubMed

Insights

Oncolytic virotherapy using Urabe mumps virus (MuV) shows promise for triple-negative breast cancer (TNBC). Specific MuV isolates effectively killed cancer cells in vitro and in vivo, paving the way for clinical trials.

Area of Science:

  • Oncolytic Virotherapy
  • Cancer Research
  • Virology

Background:

  • The clinical utility of oncolytic virotherapy was initially shown in Japanese trials using Urabe mumps virus (MuV) in the 1970s and 1980s.
  • Analysis of the original MuV clinical trial stock (MuV-U-Japan) revealed closely related MuV variants.

Purpose of the Study:

  • To evaluate the efficacy of MuV-U-Japan isolates against triple-negative breast cancer (TNBC).
  • To assess the potential of MuV-UC for translation into modern clinical applications for TNBC treatment.

Main Methods:

  • In vitro and in vivo testing of MuV-U-Japan isolates (MuV-UA and MuV-UC) against human breast cancer cell lines and TNBC xenografts.
  • Evaluation of MuV-UC activity against patient-derived xenograft (PDX) cell lines and organoids, including chemotherapy-resistant models.
  • Development of a large-scale MuV-U production and purification process.

Main Results:

  • Two MuV-U-Japan isolates, MuV-UA and MuV-UC, demonstrated potent killing of breast cancer cell lines in vitro.
  • MuV-UC significantly extended survival in mice with human TNBC xenografts.
  • MuV-UC showed significant efficacy against 3D organoids derived from breast cancer PDXs, including those resistant to standard chemotherapy.

Conclusions:

  • MuV-UC exhibits potent anti-cancer activity against TNBC models, including chemotherapy-resistant variants.
  • The development of a scalable MuV-U production process supports its advancement towards clinical trials.
  • MuV-UC is a promising candidate for clinical trials in treating patients with triple-negative breast cancer.
Keywords:
MDA-MB-231 breast tumor xenograft nude mouse modelUrabe mumps virushuman breast canceroncolytic virotherapytriple-negative breast cancer

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