716 | CD19‐DIRECTED CHIMERIC ANTIGEN RECEPTOR‐CELL THERAPY FOR B‐CELL LYMPHOMAS WITH PRIMARY OR SECONDARY CNS INVOLVEMENT. REAL‐WORLD DATA FROM A MULTICENTER ANALYSIS

Le résumé fourni par la source

Objective: To transiently open the blood-brain barrier (BBB) using low-intensity focused ultrasound (LIFU) combined with microbubbles, thereby enhancing the delivery of CD20 monoclonal antibody (mAb) into the brain parenchyma, increasing intracranial drug concentration, and improving therapeutic efficacy against primary central nervous system lymphoma (PCNSL).Methods: The PCNSL model was established in 6 to 8 weeks BALB/c mice via stereotactic intracranial inoculation of murine A20 cells into the right striatum.Tumor implantation was confirmed by fluorescence imaging on day 7 post-inoculation.Thirty-two successfully implanted mice were randomly divided into four groups: Group A (no intervention), Group B (CD20 mAb alone), Group C (LIFU alone), and Group D (LIFU þ CD20 mAb).Tumor progression was monitored using in vivo imaging.Cerebrospinal fluid (CSF) was collected 2 h posttreatment to measure intracranial drug concentration.Mice were observed for two treatment cycles, followed by brain dissection for pathological analysis of BBB opening, tumor size, and ultrasound-exposed tissue integrity.Results: Group A (control): Tumors grew rapidly with extensive metastasis; mortality exceeded 75% within one week and reached 100% by the end of the observation period.Group B (CD20 mAb alone): Tumor growth slowed slightly (mean reduction: 21.3 � 2%), with no significant metastasis; intracranial drug concentration was 0.3 � 0.03%.Group C (LIFU alone): Outcomes mirrored Group A; histopathology confirmed transient BBB opening without permanent tissue damage.Group D (LIFU þ CD20 mAb): Tumors shrank significantly (mean reduction: 81.3 � 5%) within one week; intracranial drug concentration surged to 38.6 � 0.05%.Conclusion: The BBB limits the efficacy of CD20 mAb in PCNSL therapy.LIFU combined with microbubbles enables safe, transient BBB opening, significantly enhancing intracranial drug delivery and therapeutic outcomes.This approach holds promise as a novel clinical strategy for PCNSL.

Ce résumé expose les affirmations des auteurs. BNTIC ne l’interprète pas comme une validation indépendante des résultats.