A small-molecule SUMOylation inhibitor activates antitumor immune responses and potentiates immune therapies in preclinical models
Eric S. Lightcap, Pengfei Yu, Stephen Grossman, Keli Song, Mithun Khattar, Kristina Xega, Xingyue He, James M. Gavin, Hisashi Imaichi, James Garnsey, Erik Koenig, Hongru Zhang, Zhen Lu, Pooja Shah, Yu Fu, Michael A. Milhollen, Beryl A. Hatton, Jessica Riceberg, Vaishali Shinde, Cong Li, James Minissale, Xiaofeng Yang, Dylan B. England, Richard A. Klinghoffer, Steven Langston, Katherine Galvin, Gary Shapiro, Sai Murali Krishna Pulukuri, Serge Y. Fuchs, Dennis Huszar
Abstract
T cells, and associated with increased intratumoral T and natural killer cell number and activation. Combination of TAK-981 with anti-PD1 or anti-CTLA4 antibodies improved the survival of mice bearing syngeneic CT26 and MC38 tumors. In conclusion, TAK-981 is a first-in-class SUMOylation inhibitor that promotes antitumor immune responses through activation of IFN1 signaling. TAK-981 is currently being studied in phase 1 clinical trials (NCT03648372, NCT04074330, NCT04776018, and NCT04381650) for the treatment of patients with solid tumors and lymphomas.