TY - JOUR
T1 - Oncolytic Urabe mumps virus
T2 - A promising virotherapy for triple-negative breast cancer
AU - Behrens, Marshall D.
AU - Stiles, Robert J.
AU - Pike, Gennett M.
AU - Sikkink, Laura A.
AU - Zhuang, Yongxian
AU - Yu, Jia
AU - Wang, Liewei M
AU - Boughey, Judy C.
AU - Goetz, Matthew Philip
AU - Federspiel, Mark J.
N1 - Funding Information:
Funding was provided by the Mayo Clinic Breast SPORE , NIH CA11620 1, the Mayo Clinic Department of Molecular Medicine , and the Mayo Foundation . We thank all members of the Mayo Clinic VVPL , especially Sharon Stephan and Deborah Melder , for invaluable support and conducting assays for the project.
Publisher Copyright:
© 2022 The Authors
PY - 2022/12/15
Y1 - 2022/12/15
N2 - 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.
AB - 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.
KW - human breast cancer
KW - MDA-MB-231 breast tumor xenograft nude mouse model
KW - oncolytic virotherapy
KW - triple-negative breast cancer
KW - Urabe mumps virus
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U2 - 10.1016/j.omto.2022.11.002
DO - 10.1016/j.omto.2022.11.002
M3 - Article
AN - SCOPUS:85142726858
VL - 27
SP - 239
EP - 255
JO - Molecular Therapy - Oncolytics
JF - Molecular Therapy - Oncolytics
SN - 2372-7705
ER -