Develop a novel therapy with immuno- and onco-targeting dual efficacies to treat the triple negative breast cancer

While with the recent breakthrough in immunotherapy, which has transformed into a standard care for therapy in treatment of many advanced cancers, cancer remains as the second leading cause of death. This is in part due to the efficacy of cancer immunotherapy is still limited in treatment of most solid tumors and often associated with immunotherapy-related adverse events with multiple tissues/organs autoimmune inflammation. Clinicians have attempted combinations of cancer immunotherapy with either irradiation or chemotherapies to achieve synergistic efficacy and reduce their toxicities. However, one of the obstacles is that many of the chemotherapeutic drugs, if not all, often have immune toxicities, and their administration largely reduces the immune cell frequency in the circulating blood, which consequently impairs antitumor immunity and diminishes immune checkpoint blockade therapeutic efficacy. Another urgent need in cancer therapy is to improve the therapeutic efficacy to target cancer stem cells, which drive cancer inhiation, metastasis and recurrence. Therefore, it will be ideal to develop an antitumor strategy with both chemo-targeting and immuno-activating therapeutic efficacy and also can target cancer stem cells. Importantly, our recent publications and preliminary studies revealed that USP22 functions as an oncogene in tumor cells and inhibits immune surveillance. Genetic USP22 suppression inhibits cancer cell growth, impair cancer cell stemness and boost antitumor immunity. The current application from Northwestern University (NU) and an industry partner, the startup company ExoMira, with the service based support from a world-leading chemistry company WuXi AppTec aims to develop IND-enabling study of a first-in-class medicine, USP22- specific small molecule inhibitor, for the treatment of triple negative breast cancer.