Functional antibodies produced by oncolytic clostridia.
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-1alpha) 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-1alpha. 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.
Groot
Arjan J
AJ
Department of Pathology, University Medical Centre Utrecht, P.O. Box 85500, 3508 GA, Utrecht, The Netherlands.
Mengesha
Asferd
A
van der Wall
Elsken
E
van Diest
Paul J
PJ
Theys
Jan
J
Vooijs
Marc
M
D000907:Antibodies, Bacterial / Q000276:immunology*; D003013:Clostridium / Q000145:classification* / Q000276:immunology*; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000276:immunology*; D009369:Neoplasms / Q000276:immunology* / Q000382:microbiology*; D013045:Species Specificity
D000907:Antibodies, Bacterial; C497442:HIF1A protein, human; D051795:Hypoxia-Inducible Factor 1, alpha Subunit