Xenetic Biosciences DNase I Boosts CAR-T Persistence, Tumor Control and Survival in Models
XBIO•In NALM-6 and Raji xenograft models, DNase I co-therapy enhanced CAR-T persistence, delayed relapse and prolonged survival versus CAR-T alone. Translational data in a refractory pediatric Burkitt lymphoma case showed marked CAR-T expansion and tumor burden reduction following DNase I adjunct treatment.
1. Preclinical Efficacy in Xenograft Models
In NALM-6 B cell leukemia and Raji Burkitt lymphoma xenograft models, DNase I combined with CAR-T therapy significantly improved tumor control, delayed relapse upon rechallenge and prolonged survival compared to CAR-T treatment alone.
2. DNase I Mechanism and Cellular Impact
DNase I degrades extracellular DNA and neutrophil extracellular traps (NETs), preserving CAR-T effector function, improving CD8-positive T cell ratios and reducing exhaustion markers such as PD-1, LAG-3 and TIM-3 across multiple in vitro tumor rechallenge rounds.
3. Pediatric Case Translational Data
In a pediatric patient with highly refractory Burkitt lymphoma, co-administration of DNase I was associated with marked CAR-T cell expansion and progressive tumor burden reduction following prior CAR-T failure, demonstrating translational potential in a clinical setting.
4. Clinical Development Outlook
These findings support continued clinical development of DNase I as an adjunctive immuno-oncology strategy to augment existing CAR-T therapies and address NET-driven immune suppression in difficult-to-treat hematologic malignancies.
