The science
A hallmark of many cancers is the elevated blood cfDNA. CLS Therapeutics was the first to make the breakthrough discovery showing that the destruction of serum cfDNA holds promise in cancer treatment, contributing to the decrease of primary tumor growth and metastasis formation.
Based on these discoveries by CLS Therapeutics founders and additional research from leading scientific groups, we are advancing first-in-class anticancer gene therapy, CLS-014, to disrupt circulating cfDNA. We believe this therapy may hold the potential to combat a wide range of tumors where elevated cfDNA has a biological significance in appearance and progression.
Circulating “cell-free DNA” (cfDNA) is DNA which freely circulates in the bloodstream. In tumor patients the blood level of cfDNA is increased because of the release or section of cfDNA from the tumor cells as well as from neutrophils due to an altered immune response. These cfDNA is readily taken up by a variety of healthy cells triggering their malignization and metastasis formation.
Plasma DNase I activity
DNase I is an enzyme that circulates in the blood and actively protects healthy cells from circulating cfDNA. Patients with pancreatic, liver, and stomach cancers have a decreased DNase I activity.
Thus, along with the elevated levels of cfDNA that is released and secreted during cancerogenesis, the reduced DNase I activity also leads to increased blood cfDNA levels.
CLS-014 is the first gene therapy drug designed to increase the blood DNase I level therefore destroying circulating cancer cfDNA, inhibiting primary tumor growth and metastasis formation.
Selected Publications
High quantity of cell free DNA is associated with poor outcome in pancreatic cancer
- Chen L et al. 2018. Prognostic value of circulating cell-free DNA in patients with pancreatic cancer: A systemic review and meta-analysis.
- Lapin M et al. 2018. Fragment size and level of cell-free DNA provide prognostic information in patients with advanced pancreatic cancer. Journal of translational medicine.
- Hawes MC et al. 2015. Extracellular DNA: a bridge to cancer
- Wen F et al. 2013. Extracellular DNA in pancreatic cancer promotes cell invasion and metastasis
- Fuchs TA et al. 2010. Extracellular DNA traps promote thrombosis
- Demers M et al. 2012. Cancers predispose neutrophils to release extracellular DNA traps that contribute to cancer-associated thrombosis
- Niu Z et al. 2018. Cell-free DNA derived from cancer cells facilitates tumor malignancy through Toll-like receptor 9 signaling-triggered interleukin-8 secretion in colorectal cancer.
Pancreatic, liver and stomach cancers are characterized by elevated levels of cfDNA, which plays a crucial role in their progression.
More detail on selected cancers
