Bolt-on Chimeric Receptor
Scientists have discovered that the tumor microenvironment in many solid tumor cancers is highly immunosuppressive, blocking T cells from functioning as they should.
To address this issue, Unum has developed a new technology called BOXR, or Bolt-on Chimeric Receptor, to discover and incorporate “bolt-on” transgenes to enhance intrinsic T cell functionality and overcome multiple mechanisms of immunosuppression in the solid tumor microenvironment.
Unique Platform to Interrogate T cell Biology
Unum’s BOXR discovery platform is designed to broadly evaluate T cell phenotypes through a rigorous, multi-stage screening strategy that simulates the tumor microenvironment. Unum has discovered and continues to enrich a library of master regulatory genes of T cell biology that regulate pathways essential for cell growth, proliferation, and survival under a variety of conditions.
The BOXR bolt-on transgenes identified in this platform can address a variety of immunosuppressive mechanisms of solid tumors, including metabolic competition, immune suppressor cells and exhaustion due to chronic stimulation. Once discovered, BOXR transgenes may be incorporated into many different types of therapeutic T cells, including both ACTR T cells and CAR-T cells, to impart new functionality to T cell therapies.
Using a variety of BOXR bolt-on transgenes and tumor targeting technologies, Unum is building a pipeline of product candidates to address a diverse range of solid tumor indications.
BOXR1030, the first preclinical product candidate to emerge from the BOXR platform, is composed of a GPC3 targeted CAR and a “bolt-on” enzyme called glutamic-oxaloacetic transaminase 2 (GOT2) that aims to improve T cell function in the solid tumor microenvironment through enhanced metabolism. GOT2 plays a central metabolic role by linking multiple pathways involved in biosynthesis and cellular energy production.
In our preclinical studies representing the immunosuppressive tumor microenvironment, GOT2 displayed pleiotropic effects on BOXR1030 T cells, dramatically improving anti-tumor activity beyond that achieved with traditional CAR-T cells.