title: Macrophage delivery of an oncolytic virus abolishes tumor regrowth and metastasis after chemotherapy or irradiation.
abstract: Frontline anticancer therapies such as chemotherapy and irradiation often slow tumor growth, but tumor regrowth and spread to distant sites usually occurs after the conclusion of treatment. We recently showed that macrophages could be used to deliver large quantities of a hypoxia-regulated, prostate-specific oncolytic virus (OV) to prostate tumors. In the current study, we show that administration of such OV-armed macrophages 48 hours after chemotherapy (docetaxel) or tumor irradiation abolished the posttreatment regrowth of primary prostate tumors in mice and their spread to the lungs for up to 27 or 40 days, respectively. It also significantly increased the lifespan of tumor-bearing mice compared with those given docetaxel or irradiation alone. These new findings suggest that such a novel, macrophage-based virotherapy could be used to markedly increase the efficacy of chemotherapy and irradiation in patients with prostate cancer.
authors.affiliation: Academic Unit of Inflammation & Tumor Targeting, University of Sheffield Medical School, Sheffield, United Kingdom.
authors.forename: Munitta
authors.initials: M
authors.lastname: Muthana
authors.forename: Samuel
authors.initials: S
authors.lastname: Rodrigues
authors.forename: Yung-Yi
authors.initials: YY
authors.lastname: Chen
authors.forename: Abigail
authors.initials: A
authors.lastname: Welford
authors.forename: Russell
authors.initials: R
authors.lastname: Hughes
authors.forename: Simon
authors.initials: S
authors.lastname: Tazzyman
authors.forename: Magnus
authors.initials: M
authors.lastname: Essand
authors.forename: Fiona
authors.initials: F
authors.lastname: Morrow
authors.forename: Claire E
authors.initials: CE
authors.lastname: Lewis
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage; D045744:Cell Line, Tumor; D003131:Combined Modality Therapy; D000077143:Docetaxel; D006801:Humans; D008175:Lung Neoplasms / Q000556:secondary / Q000628:therapy; D008264:Macrophages / Q000821:virology*; D008297:Male; D051379:Mice; D050130:Oncolytic Virotherapy / Q000379:methods*; D011471:Prostatic Neoplasms / Q000532:radiotherapy / Q000628:therapy*; D012008:Recurrence; D043823:Taxoids / Q000008:administration & dosage*; D023041:Xenograft Model Antitumor Assays
chemical_list: D000970:Antineoplastic Agents; D043823:Taxoids; D000077143:Docetaxel