Exth-04. cytostatic hypothermia against glioblastoma and the development of a neural implant for rodents and swine

Abstract Survival rates for patients with glioblastoma (GBM) remain discouraging due to the near-impossibility of eradicating all tumor cells, resulting in frequent recurrence. However, studies have shown that recurrence is predominantly localized (80% of cases) and that survival outcomes are improved with supra-total resection. Consequently, non-destructive local therapies hold promise for preventing GBM recurrence. We have demonstrated that non-freezing, 'cytostatic' hypothermia is a unique and effective approach against GBM. Unlike ablative cryogenic hypothermia, which kills both neoplastic and healthy infiltrated tissue, this method safely and effectively inhibits GBM growth. Through extensive investigations, we have previously identified a cytostatic window of 20–25°C and examined its impact on multiple pathways. By implementing hypothermia, we successfully inhibited GBM growth, doubling median survival in two rodent models. Notably, all rats subjected to cytostatic hypothermia survived the study period. To further advance towards translation, we conducted computer simulations to demonstrate the feasibility of a scaled and implantable system. Subsequently, we designed and fabricated a multiprobe array capable of uniformly extracting heat from a small volume of brain tissue in swine. This heat would then be transferred to the dorsal flank through an innovative artificial internal circulation system (AICS). The system underwent iterative testing in vitro and validation in vivo using live, anesthetized swine. Unlike targeted therapeutics that often show promise in preclinical models but fail in clinical trials, cytostatic hypothermia capitalizes on fundamental physics that broadly influence biology. It has the potential to reduce brain tumor recurrence, limit tumor evolution, and simultaneously offer time to patients as other cytotoxic therapies are developed.