Engineering programmable CAR and antigen pairing via drug-gated light activation - PubMed
4 hours ago
- #immunotherapy
- #CAR-T therapy
- #solid tumors
- Engineered a high-affinity R-phycoerythrin (PE)-binding monobody for PE-programmable CAR targeting user-defined antigens.
- Developed a drug-gated light-activation (DGLA) strategy to spatially confine CAR function and reduce off-tumor toxicity.
- Combined DGLA with synNotch-mediated programmable antigen-targeting CAR (sPAT) to create DGLA-sPAT for programmable CAR-antigen pairing.
- DGLA-sPAT induces clinically validated antigens on tumor cells as 'training centers' to recruit and activate sPAT CAR T cells.
- Demonstrated local T cell activation and potent tumor suppression in vivo with minimal off-tumor toxicity.
- Provides a modular and spatially controlled framework to address antigen escape and heterogeneity in solid-tumor CAR-T therapy.