Functional antibodies produced by oncolytic clostridia

Arjan J. Groot, Asferd Mengesha, Elsken van der Wall, Paul J.van Diest, Jan Theys, Marc Vooijs

Research output: Contribution to journalArticlepeer-review

Abstract

Hypoxia is a hallmark of solid cancer and characterized by regions of low oxygen and necrosis due to insufficient blood perfusion. Intratumoral hypoxia triggers the transcription of genes responsible for cell survival. The transcription factor hypoxia-inducible factor 1alpha (HIF-1α) is a key regulator of this response. HIF activation is associated with resistance to radio-and chemotherapy and poor clinical outcome, and may therefore provide an attractive therapeutic target. Clostridium-based oncolysis is a promising therapeutic strategy for the treatment of hypoxic tumors where these microorganisms naturally home. Here, we report for the first time the isolation of transconjugants of two excellent tumor colonizing Clostridium strains, C. novyi-NT and C. sporogenes, expressing single chain antibodies specific for human HIF-1α. This is a first step towards Clostridium-directed antibody therapy (CDAT) that holds promise as a carrier of cancer therapeutics targeting the most resistant regions in human solid cancer.

Original languageEnglish (US)
Pages (from-to)985-989
Number of pages5
JournalBiochemical and Biophysical Research Communications
Volume364
Issue number4
DOIs
StatePublished - Dec 28 2007

Keywords

  • Bacteria
  • Cancer
  • Clostridium
  • HIF-1α
  • Hypoxia
  • VHH

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

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