As we said in our opening post, our intention for this blog is to share news and analysis related to plant-based recombinant expression systems and how our work at Ventria Bioscience fits into the broader context of global public health. To kick things off, we’re going to take a look back at a recent journal article from the Journal of Crohn’s and Colitis, about one of our candidate therapeutics, VEN120. This publication was the result of a multi-year collaboration between Ventria Bioscience Inc. and a group of researchers led by Edwin de Zoeten MD, PhD, Associate Professor of Pediatrics at the University of Colorado School of Medicine and Scientific Director at the Children’s Hospital of Colorado Inflammatory Bowel Disease Center.
The principal active component of VEN120 is a recombinant form of the human lactoferrin protein (rhLactoferrin), which Ventria Bioscience produces using our plant-based expression system, ExpressTec. Naturally occurring human lactoferrin is an important component of breastmilk and other mucosal fluids such as saliva, tears, and nasal secretions. Importantly, this orally available protein has been shown to be an essential component of the innate immune system and to promote gut health in infants.
The research described in the Journal of Crohn’s and Colitis, published in May of 2017, explored the ability of VEN120 to modulate the immune response in two mouse models of inflammatory bowel disease (IBD). In humans, IBD is a family of related diseases that includes Crohn’s disease and ulcerative colitis, and is characterized by chronic and often debilitating inflammation of the digestive tract.
The study investigators, who included Ventria Bioscience employees Randall Alfano, PhD and Chris MacManus PhD, found that, when administered orally, VEN120 was able to reduce inflammation in both the dextran sodium sulphate colitis model and the TNFΔARE/+ model of ileitis.1
Flow cytometric analysis of T cell populations within the lamina propria (gut lining) and mesenteric lymph nodes showed that VEN120 treatment was associated with increases in the number of anti-inflammatory regulatory T cells (Treg) in the intestinal lining. In vitro, treatment of CD4+T cells with VEN120 resulted in an upregulation of genes associated with the Treg phenotype, and a skew of T cell population balance towards Tregs, with increased associated cellular homing to the intestinal lamina propria and associated lymph tissue in healthy mice.
Together, these findings demonstrate that VEN120 modulates T cells to control T cell-driven inflammatory disease by a previously undescribed mechanism. They pave the way for human clinical studies, and the promise of a potentially new, orally administered therapy for alleviating the symptoms of the millions of people who suffer from IBD and associated gut conditions.
- MacManus CF, Collins CB, Nguyen TT, Alfano RW, Jedlicka P, de Zoeten EF. VEN-120, a recombinant human lactoferrin, promotes a regulatory t cell [Treg] phenotype and drives resolution of inflammation in distinct murine models of inflammatory bowel disease. J Crohns Colitis. 2017;11(9):1101-1112.