{"doi":"10.1016/j.omto.2022.11.002","title":"Oncolytic Urabe mumps virus: A promising virotherapy for triple-negative breast cancer","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. 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.","journal":"Molecular Therapy — Oncolytics","year":2022,"id":260397,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":16,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9581,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2022-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":913668,"name":"Robert J. Stiles","orcid":"0000-0001-8794-0019","position":1,"is_corresponding":false},{"id":914100,"name":"Gennett M. Pike","orcid":null,"position":2,"is_corresponding":false},{"id":914101,"name":"Laura A. Sikkink","orcid":null,"position":3,"is_corresponding":false},{"id":498785,"name":"Yongxian Zhuang","orcid":"0000-0001-8219-7764","position":4,"is_corresponding":false},{"id":270358,"name":"Jia Yu","orcid":"0000-0001-8342-5423","position":5,"is_corresponding":false},{"id":228987,"name":"Liewei Wang","orcid":"0000-0003-3818-8531","position":6,"is_corresponding":false},{"id":242408,"name":"Judy C. Boughey","orcid":"0000-0003-3820-3228","position":7,"is_corresponding":false},{"id":232394,"name":"Matthew P. Goetz","orcid":"0000-0002-4383-270X","position":8,"is_corresponding":false},{"id":899629,"name":"Mark J. Federspiel","orcid":"0000-0002-3713-186X","position":9,"is_corresponding":false},{"id":914099,"name":"Marshall D. Behrens","orcid":null,"position":0,"is_corresponding":true}],"reference_count":30,"raw_metadata":null,"created_at":"2026-07-19T00:26:03.189798Z","pmid":"36458203","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}