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bioRxiv · 10.1101/2020.07.27.223206

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

Sheybani, N. D.·Paul, S.·McCauley, K. S.·Breza, V.·Berr, S. S.·Miller, G. W.·Neumann, K. D.·Price, R. J.
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Abstract

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 [89Zr]-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.

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Sheybani, N. D., Paul, S., McCauley, K. S., Breza, V., Berr, S. S., Miller, G. W., Neumann, K. D., Price, R. J.. 2020-07-29. ImmunoPET-informed sequence for focused ultrasound-targeted mCD47 blockade controls glioma. https://doi.org/10.1101/2020.07.27.223206

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