VAX014 Activates Tumor-Intrinsic STING and RIG-I to Promote the Development of Antitumor Immunity.

ABSTRACT: In situ immunization (ISI) has emerged as a promising approach to bolster early phases of the cancer immunity cycle through improved T-cell priming. One class of ISI agents, oncolytic viruses (OV), has demonstrated clinical activity, but overall benefit remains limited. Mounting evidence suggests that due to their inherent vulnerability to antiviral effects of type I IFN, OVs have limited activity in solid tumors expressing stimulator of interferon genes (STING) and/or retinoic acid-inducible gene I (RIG-I). Here, using a combination of pharmacologic, genetic, and in vivo approaches, we demonstrate that VAX014, a bacterial minicell-based oncolytic ISI agent, activates both STING and RIG-I and leverages this activity to work best in STING-positive and/or RIG-I-positive tumors. Intratumoral

SUBMITTER: Nelson KL 

PROVIDER: S-EPMC11962400 | biostudies-literature | 2025 Apr

REPOSITORIES: biostudies-literature