Preclinical safety assessment of MV-s-NAP, a novel oncolytic measles virus strain armed with an H. pylori immunostimulatory bacterial transgene

Kimberly B. Viker, Michael B. Steele, Ianko D. Iankov, Susanna C. Concilio, Arun Ammayappan, Brad Bolon, Nathan J. Jenks, Matthew P. Goetz, Eleni Panagioti, Mark J. Federspiel, Minetta C. Liu, Kah Whye Peng, Evanthia Galanis

Research output: Contribution to journalArticlepeer-review


Despite recent therapeutic advances, metastatic breast cancer (MBC) remains incurable. Engineered measles virus (MV) constructs based on the attenuated MV Edmonston vaccine platform have demonstrated significant oncolytic activity against solid tumors. The Helicobacter pylori neutrophil-activating protein (NAP) is responsible for the robust inflammatory reaction in gastroduodenal mucosa during bacterial infection. NAP attracts and activates immune cells at the site of infection, inducing expression of pro-inflammatory mediators. We engineered an MV strain to express the secretory form of NAP (MV-s-NAP) and showed that it exhibits anti-tumor and immunostimulatory activity in human breast cancer xenograft models. In this study, we utilized a measles-infection-permissive mouse model (transgenic IFNAR KO-CD46Ge) to evaluate the biodistribution and safety of MV-s-NAP. The primary objective was to identify potential toxic side effects and confirm the safety of the proposed clinical doses of MV-s-NAP prior to a phase I clinical trial of intratumoral administration of MV-s-NAP in patients with MBC. Both subcutaneous delivery (corresponding to the clinical trial intratumoral administration route) and intravenous (worst case scenario) delivery of MV-s-NAP were well tolerated: no significant clinical, laboratory or histologic toxicity was observed. This outcome supports the safety of MV-s-NAP for oncolytic virotherapy of MBC. The first-in-human clinical trial of MV-s-NAP in patients with MBC ( NCT04521764) was subsequently activated.

Original languageEnglish (US)
Pages (from-to)532-546
Number of pages15
JournalMolecular Therapy - Methods and Clinical Development
StatePublished - Sep 8 2022


  • IFNAR KO-CD46Ge mouse model
  • MV-s-NAP
  • NAP
  • measles
  • metastatic breast cancer
  • neutrophil activating protein
  • oncolytic virus

ASJC Scopus subject areas

  • Molecular Medicine
  • Molecular Biology
  • Genetics


Dive into the research topics of 'Preclinical safety assessment of MV-s-NAP, a novel oncolytic measles virus strain armed with an H. pylori immunostimulatory bacterial transgene'. Together they form a unique fingerprint.

Cite this