Objective: DARTRIX, DARPin Targeted RX (therapy) is a multidisciplinary collaborative project that will develop high-affinity protein scaffolds to create a new generation of targeted therapeutics for the treatment of glioblastoma. There is great need; glioblastoma is virtually incurable and most patients die within 12 months of diagnosis.
DARPins (find detail) are small, non-immunoglobulin human protein scaffolds that bind specific targets with exceptionally high-affinity. DARPins are amenable to GMP production and to scale-up. They are remarkably stable, even at high temperatures and they can be engineered to incorporate additional favourable properties to target glioblastoma cells with exceptionally high affinity.
The new DARPins will be coupled to ferucarbotran, an FDA-approved contrast agent for Magnetic Resonance Imaging (MRI). So it is safe to use in patients and can be traced in the body. When stimulated by an appropriate alternating magnetic current, ferucarbotran generates heat that can kill cancer cells very effectively. The conjugation of DARPins with ferucarbotran (DARTRIX particle) leads to a potent therapeutic for thermal ablation of glioblastoma.
In addition, DARTRIX particle will be created economically, exploiting the fact that DARPins can be produced to GMP in gram quantities using E. coli. The DARTRIX particles will target to glioblastoma cells by virtue of the high affinity and specificity of DARPins and the particles will remain in place when heated. By using DARPins to target the DARTRIX particle to tumour cells before application of the magnetic current, it should be possible to generate toxic heat specifically in the tumour. The consortium has all the skills and knowledge to develop DARPins from bench-to-bedside for glioblastoma treatment.
This DARTRIX particle will pioneer targeted hyperthermic cancer treatment of glioblastoma in an innovative adaptive first-in-man trial, using localised convection enhanced delivery.