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

Marshall D. Behrens, Robert J. Stiles, Gennett M. Pike, Laura A. Sikkink, Yongxian Zhuang, Jia Yu, Liewei M Wang, Judy C. Boughey, Matthew Philip Goetz, Mark J. Federspiel

Research output: Contribution to journalArticlepeer-review

Abstract

Historically, the clinical utility of oncolytic virotherapy as a treatment for a wide range of cancer types was first demonstrated by three pilot human clinical trials conducted in Japan in the 1970s and 1980s using a wild-type Urabe mumps virus (MuV) clinical isolate. Using a sample of the actual original oncolytic Urabe MuV clinical trial virus stock (MuV-U-Japan) used in these Japanese clinical trials, we found that MuV-U-Japan consisted of a wide variety of very closely related Urabe MuVs that differed by an average of only three amino acids. Two MuV-U-Japan isolates, MuV-UA and MuV-UC, potently killed a panel of established human breast cancer cell lines in vitro, significantly extended survival of nude mice with human triple-negative breast cancer (TNBC) MDA-MB-231 tumor xenografts in vivo, and demonstrated significant killing activity against breast cancer patient-derived xenograft (PDX) cell lines grown as 3D organoids, including PDXs from patients resistant to anthracycline- and taxane-based chemotherapy. We also report success in developing a large-scale MuV-U production and purification process suitable for supporting Investigational New Drug applications for clinical trials. This study demonstrates the suitability of the MuV-UC virus for translation to modern clinical trials for treating patients with TNBC.

Original languageEnglish (US)
Pages (from-to)239-255
Number of pages17
JournalMolecular Therapy - Oncolytics
Volume27
DOIs
StatePublished - Dec 15 2022

Keywords

  • human breast cancer
  • MDA-MB-231 breast tumor xenograft nude mouse model
  • oncolytic virotherapy
  • triple-negative breast cancer
  • Urabe mumps virus

ASJC Scopus subject areas

  • Molecular Medicine
  • Oncology
  • Cancer Research
  • Pharmacology (medical)

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