Date: 6th August 2020
A balanced immune system is critical for maintaining a healthy immune response. However, the immune system can often turn upon itself, attacking the cells and tissues within the body causing a range of autoimmune and inflammatory diseases. Yesterday saw the announcement of the launch of GentiBio, an emerging biotherapeutics company, who are developing engineered regulatory T cells (engTregs) programmed to treat autoimmune, alloimmune, autoinflammatory, and allergic diseases.
GentiBio, based in Boston, US, secured $20 million seed funding led by OrbiMed, Novartis Venture Fund and RA Capital Management, L.P. The company was co-founded by pioneers from Seattle Children’s Research Institute, Benaroya Research Institute at Virginia Mason (BRI), and MIGAL Galilee Research Institute (MIGAL), namely Adel Nada, David Rawlings, Jane Buckner and Gidi Gross – experts in Treg biology and synthetic immunology. GentiBio has licensed the ground-breaking technology from these institutes to address the technical bottlenecks that have inhibited Treg therapeutics, creating less costly and cumbersome therapies for patients in need.
The GentiBio team aim to engineer cell therapies that are equipped with the key properties needed to successfully restore immune tolerance in the body and overcome the major limitations in existing T regulatory cell-based therapeutics.
The science behind the announcement was published in the Science Translational Medicine journal, in June, led by Rawlings and Buckner. Thymic regulatory T cells (Tregs) are potent inhibitors of autoreactive immune responses, and defects in these cells are implicated in multiple autoimmune diseases, leading to growing interest in use of Tregs as cell therapies to establish immune tolerance. However, these cells appear in low concentrations in the blood which has therefore inhibited their use as therapeutics.
To overcome this bottleneck the team designed an alternative strategy to create autologous Tregs from easily accessible CD4+ T cells. The team used homology-directed repair (HDR)–based gene editing to enforce expression of FOXP3, the master transcription factor for Tregs. The resulting engTregs were able to mediate immunosuppression in vivo in models of inflammatory disease.
Further engineering with antigen specific moieties can be used to selectively restrict inflammation temporally and spatially in specific tissues, making this a powerful, tuneable therapeutic.
It is hoped the platform will accelerate the development of new therapeutics to treat and cure a variety of diseases. Autoimmune diseases are a family of more than 80 chronic and often debilitating conditions which impact around 23 million people in the US alone, it is hope this technology will transform patients health.