Dr Alexandra Mowday

BSc, MSc, PhD

Biography

Postdoctoral research fellow at the Auckland Cancer Society Research Centre and member of the Translational Therapeutics Team led by Associate Professor Adam Patterson.

Research | Current

Tumour necrosis is a typical histological feature of solid cancers that is associated with high-risk tumour characteristics and poor patient survival. Currently no therapeutic modality exists to address this clinical problem, yet necrosis offers the most desirable of all attributes for targeted therapy – absolute specificity for neoplasia (being categorically absent in normal healthy tissues). Live biotherapeutics employing bacterial vectors is a rapidly advancing area of experimental oncology and has been described as ‘the perfect cancer therapy’. Of the available platforms, the strict anaerobic bacteria Clostridum sporogenes exhibits an overt preference for necrotic tissues and is the most intrinsically selective for solid tumours. The germination of endospores is restricted to anaerobic environments whilst the vegetative bacteria are killed by direct exposure to oxygen. This offers a unique opportunity to turn a pathological feature associated with treatment failure into a precision therapy.

Low inherent anti-tumour activity of C. sporogenes necessitates development of ‘armed’ vectors; an approach termed Clostridium Directed Enzyme Prodrug Therapy (CDEPT). However to date progress has been hampered by challenges associated with stable genetic modification of the bacterial genome. This limitation has recently been overcome, allowing (for the first time) the opportunity for development of clinical grade endospore preparations compatible with medical authority regulatory requirements. As part of an international multidisciplinary collaboration, we have isolated a library of metabolically flexible bacterial nitroreductase (NTR) genes able to perform multiple functions via a single gene product; metabolism of NTR-specific PET imaging agents (for whole body vector visualisation) as well as preclinical chemotherapy prodrugs (for conditional enhancement of efficacy). We now seek to develop an NTR-armed C. sporogenes therapeutic product suitable for advancement to clinical testing. 

Current research is supported by a Health Research Council of New Zealand project grant titled ‘Colonising tumour necrosis with Clostridium sporogenes for precision therapy’. 

Distinctions/Honours

2014: Brett Roche Memorial Award, Auckland Cancer Society

2011: Doctoral Scholarship, University of Auckland

2009: Faculty of Science Masters award, University of Auckland 

Areas of expertise

  • Cancer gene therapy (GDEPT, CDEPT)
  • Clostridium sporogenes
  • Oncolytic viruses
  • Tumour necrosis
  • Cancer drug development
  • Nitrogen mustard prodrugs
  • Bacterial nitroreductases
  • Gene therapy imaging modalities

Committees/Professional groups/Services

2014-Present: Affiliate Investigator, Maurice Wilkins Centre for Molecular Biodiscovery

Selected publications and creative works (Research Outputs)