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 Wang; Judy C. Boughey; Matthew P. Goetz; Mark J. Federspiel

Molecular Therapy: Oncolytics (Dec 2022)

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 Wang,
Judy C. Boughey,
Matthew P. Goetz,
Mark J. Federspiel

Affiliations

Marshall D. Behrens: Department of Molecular Medicine, Mayo Clinic, 200 First Street, SW, Rochester, MN 55905, USA
Robert J. Stiles: Department of Molecular Medicine, Mayo Clinic, 200 First Street, SW, Rochester, MN 55905, USA
Gennett M. Pike: Department of Molecular Medicine, Mayo Clinic, 200 First Street, SW, Rochester, MN 55905, USA; Viral Vector Production Laboratory, Mayo Clinic, 200 First Street, SW, Rochester, MN 55905, USA
Laura A. Sikkink: Viral Vector Production Laboratory, Mayo Clinic, 200 First Street, SW, Rochester, MN 55905, USA
Yongxian Zhuang: Department of Molecular Pharmacology and Experimental Therapeutics, Mayo Clinic, 200 First Street, SW, Rochester, MN 55905, USA
Jia Yu: Department of Molecular Pharmacology and Experimental Therapeutics, Mayo Clinic, 200 First Street, SW, Rochester, MN 55905, USA
Liewei Wang: Department of Molecular Pharmacology and Experimental Therapeutics, Mayo Clinic, 200 First Street, SW, Rochester, MN 55905, USA
Judy C. Boughey: Department of Surgery, Mayo Clinic, 200 First Street, SW, Rochester, MN 55905, USA
Matthew P. Goetz: Department of Molecular Pharmacology and Experimental Therapeutics, Mayo Clinic, 200 First Street, SW, Rochester, MN 55905, USA; Department of Medical Oncology, Mayo Clinic, 200 First Street, SW, Rochester, MN 55905, USA
Mark J. Federspiel: Department of Molecular Medicine, Mayo Clinic, 200 First Street, SW, Rochester, MN 55905, USA; Viral Vector Production Laboratory, Mayo Clinic, 200 First Street, SW, Rochester, MN 55905, USA; Corresponding author Mark J. Federspiel, Mayo Clinic, 200 First Street, SW, Rochester, MN 55905, USA.

Journal volume & issue: Vol. 27
pp. 239 – 255

Abstract

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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.

Published in Molecular Therapy: Oncolytics

ISSN: 2372-7705 (Online)
Publisher: Elsevier
Country of publisher: United Kingdom
LCC subjects: Medicine: Internal medicine: Neoplasms. Tumors. Oncology. Including cancer and carcinogens
Website: http://www.cell.com/molecular-therapy-family/oncolytics/latest-content

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