Qin, D., Lei, Y., Shu, P., Zhang, Y., Loh, Y.-H., Wang, Y., & Li, Q. (2025). Supercharging CAR-T cells through transcriptional and epigenetic armoring. Theranostics, 15(8), 3345–3367. https://doi.org/10.7150/thno.107908
Abstract:
Inspired by the remarkable success of CAR-T therapy in hematologic malignancies, research is increasingly focused on adapting this treatment for solid tumors. However, CAR-T efficacy remains limited due to its exhaustion and shortened persistence. Transcription factors and epigenetic modifications play pivotal roles in modulating T cell differentiation and functionality, which have been leveraged in numerous strategies to promote the formation of long-lasting memory cells with stem-like properties and supercharging CAR-T performance. This review highlights pivotal transcriptional factors, such as c-Jun and FOXO1, which enhance and sustain T cell effector function, diminishes exhaustion, and epigenetic regulators like TET2 and DNMT3A, whose knockout promotes memory T subsets formation. We explore their interconnections, downstream targets, biological impacts, and the potential application risks of certain candidates, providing a comprehensive theoretical framework for supercharging CAR-T therapies through transcriptional and epigenetic interventions.
License type:
Attribution 4.0 International (CC BY 4.0)
Funding Info:
This research / project is supported by the Agency for Science, Technology and Research (A∗STAR) - Industry Alignment Fund-Pre-Positioning Program
Grant Reference no. : H23J2a0095
This research / project is supported by the Agency for Science, Technology and Research (A∗STAR) - Competitive Research Programme
Grant Reference no. : CRP29-2022-0032