IRIS: Big data-informed discovery of cancer immunotherapy targets arising from pre-mRNA alternative splicing

Pan, Y.; Lee, A. H.; Yang, H. T.; Wang, Y.; Xu, Y.; Kadash-Edmondson, K. E.; Phillips, J.; Champhekar, A.; Puig, C.; Ribas, A.; Witte, O. N.; Prins, R. M.; Xing, Y.

doi:10.1101/843268

bioRxiv · 10.1101/843268

IRIS: Big data-informed discovery of cancer immunotherapy targets arising from pre-mRNA alternative splicing

Pan, Y.·Lee, A. H.·Yang, H. T.·Wang, Y.·Xu, Y.·Kadash-Edmondson, K. E.·Phillips, J.·Champhekar, A.·Puig, C.·Ribas, A.·Witte, O. N.·Prins, R. M.·Xing, Y.

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Abstract

Aberrant alternative splicing (AS) is widespread in cancer, leading to an extensive but largely unexploited repertoire of potential immunotherapy targets. Here we describe IRIS, a computational platform leveraging large-scale cancer and normal transcriptomics data to discover AS-derived tumor antigens for T-cell receptor (TCR) and chimeric antigen receptor T-cell (CAR-T) therapies. Applying IRIS to RNA-Seq data from 22 glioblastomas resected from patients, we identified candidate epitopes and validated their recognition by patient T cells, demonstrating IRISs utility for expanding targeted cancer immunotherapy.

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Pan, Y., Lee, A. H., Yang, H. T., Wang, Y., Xu, Y., Kadash-Edmondson, K. E., Phillips, J., Champhekar, A., Puig, C., Ribas, A., Witte, O. N., Prins, R. M., Xing, Y.. 2019-11-15. IRIS: Big data-informed discovery of cancer immunotherapy targets arising from pre-mRNA alternative splicing. https://doi.org/10.1101/843268

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