Epigenetic editing balances TCR suppression and persistence in CAR T cells - PubMed
3 hours ago
- #epigenetic editing
- #allogeneic therapy
- #CAR T cells
- The study introduces an epigenetic editing method to silence the CD3ε gene in CAR T cells, suppressing the endogenous T cell receptor (TCR) without permanent DNA changes.
- Unlike CRISPR-Cas9 or base editing, this approach is reversible and reduces the risk of graft-versus-host disease (GvHD) while allowing cells to persist longer in vivo.
- Optimized in primary T and CAR T cells, the method maintains CAR expression, activation, and effector function with minimal off-target effects.
- Epigenetic editing is proposed as a safer, non-genotoxic alternative to genome editing for developing next-generation allogeneic CAR T therapies.
- In vivo data suggest transient TCR suppression balances safety by preventing GvHD and enhances long-term efficacy compared to TCR knockout cells.