Broad-acting cancer immune response initiator is a heated research topic for improving the low treatment response rate to today’s cancer immunotherapy. Parthanatos is a pharmaceutically unexplored immunogenic necrosis that is triggered by PARP hyperactivation and executed by an efficient DNA-fragmentation mechanism. We developed a broadly acting cytotoxic agent C010DS-Zn that efficiently induced parthanatos in vitro and ex vivo, which was characterized as PARP-mediated necrotic death with characteristically massive DNA damages. Characterization of its in vivo treatment effects versus the immunosuppressive 4T1-Balb/c and immunogenic CT26-Balb/c syngeneic cancer models showed that sufficiently high intravenous C010DS-Zn treatments led to tumor suppression and robust initiation in the tumor-suppressed antitumor immune compartments such as T cells and macrophages. At lower non-anticancer doses, C010DS-Zn treatment significantly reduced macrophage content and inflammation in the 4T1 tumor. Our results demonstrate C010DS-Zn’s potential utility in immune oncology, and against macrophage-mediated inflammations such as those seen in MAS or COVID19.
Author(s): Jinhyuk Fred Chung, Zhisheng Her, Wai Mun Kong, and Qingfeng Chen