Superior In Vivo Efficacy for T Cell Engineering via Citronellol-Tailored mRNA-tLNPs - PubMed
a day ago
- #T cell engineering
- #mRNA-LNP delivery
- #CAR T cells
- Efficient in vivo generation of CAR T cells via mRNA-LNP delivery requires high-efficiency T cell engineering.
- Current systems are suboptimal, with high lymphoid tropism alone being insufficient for effective T cell transfection.
- Intrinsic T cell transfection potency is identified as a critical determinant alongside tropism.
- H3T4, a citronellol-tailed LNP, is identified for enhanced lymphoid tropism and superior intrinsic potency.
- CD3-targeted H3T4 LNP (αH3T4) achieves ~85% in vivo efficacy in T cell engineering, outperforming benchmarks by ~50%.
- Effective T cell engineering requires balancing potency and tropism, not just maximizing tropism.
- In murine CD19 solid tumor models, αH3T4-generated CAR T cells achieved 83% tumor clearance.
- Intrinsic transfection potency is established as a primary tunable parameter for next-generation CAR T platforms.