mRNA challenge predicts brain cancer immunogenicity and response to checkpoint inhibitors

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

doi:10.1101/2023.03.18.532056

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bioRxiv · 10.1101/2023.03.18.532056

mRNA challenge predicts brain cancer immunogenicity and response to checkpoint inhibitors

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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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Castillo, P., Ogando-Rivas, E., Geffrard, H., Pepe, A., Liu, R., Nguyen, D. T., Pedro, D., Zhang, D., DeVries, A., Qdaisat, S., Karachi, A., Rahman, M., Weidert, F., Milner, R., Huang, J., Ligon, J. A., Silver, N., Li, D., Lee, J.-H., Carrera-Justiz, S., Mitchell, D. A., Mendez-Gomez, H., Sawyer, W. G., Sayour, E. J.. 2023-03-23. mRNA challenge predicts brain cancer immunogenicity and response to checkpoint inhibitors. https://doi.org/10.1101/2023.03.18.532056

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