PACM-05 LEVERAGING POLYMERIC µMESH FOR SUSTAINED CHEMOTHERAPEUTIC DEPLOYMENT AGAINST SPINAL METASTASES

Abstract

Spinal metastases are a frequent complication of cancer and a significant source of morbidity, ultimately leading to decreased survival. Current treatments include systemic therapy, radiation, or surgery. Unfortunately, tumor recurrences frequently occur, and once local therapy has been exhausted, refractory disease has a dire prognosis. In this context, there is a significant need to develop novel, alternative local treatment options for rapidly progressive and treatment refractory spinal metastases. To approach this challenge, we propose the use of docetaxel (DTXL)-loaded μMESH, a porous polymer mesh platform designed for sustained local drug delivery, to suppress tumor growth and preserve neurologic function. Using a clinically relevant spinal metastasis animal model, we orthotopically implanted luciferase-tagged LL/2 and CMT-167 murine lung tumors into the lumbar spine of C57BL/6 mice followed by the local placement of μMESH-DTXL over the tumor two days later. Notably, LL/2 and CMT-167 were responsive to DTXL treatment in vitro,with an IC50 of 0.0223 and 0.1001 at 72 hours post-treatment, respectively. Amongst mice treated with μMESH-DTXL, we observed a significant reduction in tumor growth as measured by bioluminescent signal intensity compared to mice treated with empty μMESH or mock treated. Consistent with these findings, a reduction in tumor growth was similarly observed by MRI amongst mice treated with μMESH-DTXL. By leveraging an orthotopic spinal metastasis model, we are similarly able to track the longitudinal development of neurologic deficits (i.e. tail dragging, dorsal stepping, and paralysis) and observed a significant improvement in the preservation of neurologic function amongst mice treated with μMESH-DTXL. Lastly, therapeutic efficacy was similarly demonstrated with an improvement in overall survival amongst μMESH-DTXL treated mice. These findings provide translational insights into the treatment efficacy of μMESH-DTXL for spinal metastases, and provide a framework for our overarching goal of developing novel local treatments for patients with spinal metastases.