DARTRIX · DARPin Targeted Magnetic Hyperthermic Therapy for Glioblastoma

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 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 dextran-coated iron oxide nanoparticles, such as ferucarbotran or nanomag-MIP, which has been used clinically as a contrast agent for Magnetic Resonance Imaging (MRI). These ‘particles’ are safe to use in patients and are traceable within the body. When stimulated by an appropriate alternating magnetic current, the particles generate heat that can kill cancer cells very effectively. The conjugation of DARPins with ferucarbotran or nanomag-MIP (DARTRIX particle) leads to a potent therapeutic by delivering targeted hyperthermia to 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 direct injection or convection enhanced delivery to localise the particles to the tumour.