Creating a Novel Pro-drug to Selectively Eliminate Glioblastoma (Brain Cancer) without Causing Autoimmunity

Consequently, converting immunosuppressive M2-type macrophages into M1 systemically is not a safe and effective therapeutic approach against cancer. Through cleavable covalent linking of curcumin to the chemotherapeutic agent Paclitaxel (Taxol), we have created a novel prodrug (STO-1) that, upon untargeted intravenous delivery, selectively reprograms tumor-associated microglia and macrophages (TAMs), and eliminates glioblastoma (GBM) without causing autoimmunity. Demonstrating the therapeutic efficacy of STO-1, prolonged treatment of GBM-harboring mice rescued 67% of STO-1-treated mice by decimating GBM within 85 days from inoculation. In striking contrast to the M2→M1 reprogramming of TAMs, M1-type macrophages were suppressed in the spleens of STO-1- treated cancer-free mice. Therefore, STO-1 induces selective anti-tumor immunity and GBM elimination without triggering systemic autoimmune reactions.