ImmunoPET-informed sequence for focused ultrasound-targeted mCD47 blockade controls glioma

Phagocytic immunotherapies such as CD47 blockade have emerged as promising strategies for glioblastoma (GB) therapy, but the blood brain/tumor barriers (BBB/BTB) pose a persistent challenge for mCD47 delivery that can be overcome by focused ultrasound (FUS)-mediated BBB/BTB disruption. We here leverage immuno-PET imaging to determine how timing of [Zr-89] -mCD47 injection relative to FUS impacts antibody penetrance into orthotopic murine gliomas. We then design and implement a rational paradigm for combining FUS and mCD47 for glioma therapy. We demonstrate that timing of antibody injection relative to FUS BBB/BTB disruption is a critical determinant of mCD47 access, with post-FUS injection conferring superlative antibody delivery to gliomas. We also show that mCD47 delivery across the BBB/BTB with repeat sessions of FUS can significantly constrain tumor outgrowth and extend survival in glioma-bearing mice. This study generates provocative insights for ongoing pre-clinical and clinical evaluations of FUS-mediated antibody delivery to brain tumors. Moreover, our results confirm that mCD47 delivery with FUS is a promising therapeutic strategy for GB therapy.

Automated summary

Phagocytic immunotherapies, such as CD47 blockade, have shown promise in treating glioblastoma (GB). Overcoming the challenges posed by the blood brain/tumor barriers (BBB/BTB) for mCD47 delivery through focused ultrasound (FUS) is crucial. Timing of antibody injection relative to FUS BBB/BTB disruption is essential for optimal mCD47 access to gliomas. Repeat sessions of FUS can significantly constrain tumor outgrowth and extend survival in glioma-bearing mice, making mCD47 delivery with FUS a promising therapeutic strategy for GB therapy.