Targeted Doxorubicin Delivery to Brain Tumors via Minicells: Proof of Principle Using Dogs With Spontaneously Occurring Tumors as a Model.

To evaluate the safety and efficacy of EGFR targeted, doxorubicin loaded minicells to deliver doxorubicin to spontaneous brain tumors in 17 companion dogs; a comparative oncology model of human brain cancers. ^EGFRminicells_Dox were administered weekly via intravenous injection to 17 dogs with late-stage brain cancers. Biodistribution was assessed using PET and MRI. Anti-tumor response was determined using MRI, and blood samples were subject to toxicology (hematology, biochemistry) and inflammatory marker analysis. Targeted, doxorubicin-loaded minicells rapidly localized to the core of brain tumors. Complete resolution or marked tumor regression (>90% reduction in tumor volume) were observed in 23.53% of the cohort, with lasting anti-tumor responses characterized by remission in three dogs for more than two years. The median overall survival was 264 days (range 49 to 973). No adverse clinical, hematological or biochemical effects were observed with repeated administration of ^EGFRminicells_Dox (30 to 98 doses administered in 10 of the 17 dogs).