mRNA challenge predicts brain cancer immunogenicity and response to checkpoint inhibitors

P. Castillo; E. Ogando-Rivas; H. Geffrard; A. Pepe; R. Liu; D. T. Nguyen; D. Pedro; D. Zhang; A. DeVries; S. Qdaisat; A. Karachi; M. Rahman; F. Weidert; R. Milner; J. Huang; J. A. Ligon; N. Silver; D. Li; J.-H. Lee; S. Carrera-Justiz; D. A. Mitchell; H. Mendez-Gomez; W. G. Sawyer; E. J. Sayour

doi:10.1101/2023.03.18.532056

Cancer BiologybioRxivMar 18, 2023

Preprint

mRNA challenge predicts brain cancer immunogenicity and response to checkpoint inhibitors

P. Castillo, E. Ogando-Rivas, H. Geffrard, A. Pepe, R. Liu, D. T. Nguyen, D. Pedro, D. Zhang, A. DeVries, S. Qdaisat, A. Karachi, M. Rahman, F. Weidert, R. Milner, J. Huang, J. A. Ligon, N. Silver, D. Li, J.-H. Lee, S. Carrera-Justiz, D. A. Mitchell, H. Mendez-Gomez, W. G. Sawyer, E. J. Sayour

Abstract

To prospectively determine whether brain tumors will respond to immune checkpoint inhibitors (ICIs), we developed a novel mRNA vaccine as a viral mimic to elucidate cytokine release from brain cancer cells in vitro. Our results indicate that cytokine signatures following mRNA challenge differ substantially from ICI responsive versus non-responsive murine tumors. These findings allow for creation of a diagnostic assay to quickly assess brain tumor immunogenicity, allowing for informed treatment with ICI or lack thereof in poorly immunogenic settings.

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