Targeting endosomal trafficking-mediated antigen escape to resensitize myeloma to CAR-T therapy - PubMed
4 days ago
- #Antigen escape
- #CAR-T therapy
- #Multiple Myeloma
- Antigen escape is a major cause of relapse in CAR-T therapy, especially in multiple myeloma.
- RRM2+ myeloma subpopulations show reduced MICA/B surface abundance, contributing to CAR-T resistance.
- RRM2 regulates MICA/B trafficking, shuttling it toward lysosomal degradation via RAB7A activation and blocking RAB11-mediated recycling.
- Subtoxic osalmid treatment reverses trafficking defects, restoring MICA/B presentation and enhancing NKG2D CAR-T efficacy.
- Combining osalmid with NKG2D CAR-T therapy achieves durable tumor remission by sustaining T-cell fitness and reducing exhaustion.
- This strategy offers a clinically actionable solution to antigen escape in CAR-T therapy.