Abstract 467: Programmable transcription factors as protein adjuvants for cancer immunotherapy

Abstract Immunotherapies are transforming clinical oncology by exploiting immune pathways to improve cancer treatment outcomes and provide long-term remission. Anticancer immune pathways are typically activated with dose regimens of antibodies, engineered cytokines, salt or oil emulsions, oligonucleotides, or lipid nanoparticles, which ultimately induce transcription and translation of interferon-stimulated genes that instruct the immune system to respond to tumors. These and other molecular adjuvants are widely used to stimulate broad inflammatory signals but are also associated with abnormal cytokine expression levels and tissue toxicity. To address the challenge of nonspecific activation and to improve antitumor immunity, our group is developing artificial transcription factor (ATF) proteins as a generalizable technology platform to target and control specific immune signaling pathways. This presentation will describe the design and characterization of these ATF proteins, including biophysical, biological, and antitumor properties, and demonstrate their therapeutic potential as gene- and protein-based adjuvants for cancer immunotherapy. Citation Format: Nicholas Truex. Programmable transcription factors as protein adjuvants for cancer immunotherapy [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 467.