title: Vaccinia virus GLV-1h153 is effective in treating and preventing metastatic triple-negative breast cancer.
abstract: OBJECTIVE
  This study aimed to investigate the therapeutic impact of a new oncolytic vaccinia virus in a triple-negative breast cancer (TNBC) murine model and its potential for treating distant metastatic disease.
  
  
  BACKGROUND
  TNBCs are aggressive tumors associated with a high metastatic rate. Their lack of targets for hormonal/biological therapy presents significant clinical challenges and a dire need for novel therapies.
  
  
  METHODS
  GLV-1h153, a replication-competent vaccinia virus, was tested against multiple cell lines. Cytotoxicity and viral replication were determined. Intratumoral (IT) or intravenous (IV) injection of GLV-1h153 (1 × 10(7) plaque-forming units) or phosphate buffered saline was tested in an orthotopic murine model, which reliably produces systemic metastasis. Tumors, lymph nodes, and metastatic organs (lung, liver, and brain) were harvested 5 and 8 weeks after treatment and prepared for histopathological review. Demonstration of metastasis was performed using immunofluorescence and hematoxylin and eosin (H&E) staining.
  
  
  RESULTS
  GLV-1h153 infected, replicated in, and killed all TNBC cell lines in vitro. In vivo, mean tumor volume 2 weeks after treatment was 22 (IT), 29 (IV) versus 245 mm(3) (control; P < 0.002). Five weeks after treatment, all harvested lymph nodes and organs showed no evidence of metastatic cells. All harvested tumors showed complete response to treatment, with only necrosis and fibrosis on H&E staining 8 weeks after treatment.
  
  
  CONCLUSIONS
  This is the first study to demonstrate that TNBCs are killed by a novel vaccinia virus both in vitro and in vivo. Our results suggest that GLV-1h153 is a promising therapeutic agent for preventing and treating metastatic TNBC and warrants further clinical testing in patients.
authors.affiliation: Department of Surgery, Memorial Sloan-Kettering Cancer Center, New York, NY 10065, USA.
authors.forename: Sepideh
authors.initials: S
authors.lastname: Gholami
authors.forename: Chun-Hao
authors.initials: CH
authors.lastname: Chen
authors.forename: Emil
authors.initials: E
authors.lastname: Lou
authors.forename: Marina
authors.initials: M
authors.lastname: De Brot
authors.forename: Sho
authors.initials: S
authors.lastname: Fujisawa
authors.forename: Nanhai G
authors.initials: NG
authors.lastname: Chen
authors.forename: Aladar A
authors.initials: AA
authors.lastname: Szalay
authors.forename: Yuman
authors.initials: Y
authors.lastname: Fong
mesh_terms: D000818:Animals; D014408:Biomarkers, Tumor / Q000378:metabolism; D001943:Breast Neoplasms / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control / Q000628:therapy*; D045744:Cell Line, Tumor; D005260:Female; D006801:Humans; D008325:Mammary Neoplasms, Experimental / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control / Q000628:therapy*; D051379:Mice; D008819:Mice, Nude; D009362:Neoplasm Metastasis; D050130:Oncolytic Virotherapy; D050504:Oncolytic Viruses; D016896:Treatment Outcome; D014616:Vaccinia virus
chemical_list: D014408:Biomarkers, Tumor