Exome Sequencing to Predict Neoantigens in Melanoma

Antonia L. Pritchard, Julie G. Burel, Michelle A. Neller, Nicholas K. Hayward, J. Alejandro Lopez, Martina Fatho, Volker Lennerz, Thomas Woelfel, Christopher W. Schmidt

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32 Citations (Scopus)

Abstract

The ability to use circulating peripheral blood cells and matched tumor sequencing data as a basis for neoantigen prediction has exciting possibilities for application in the personalized treatment of cancer patients. We have used a high-throughput screening approach, combining whole-exome sequence data, mRNA microarrays, and publicly available epitope prediction algorithm output to identify mutated proteins processed and displayed by patient tumors and recognized by circulating immune cells. Matched autologous melanoma cell lines and peripheral blood mononuclear cells were used to create mixed lymphocyte tumor cell cultures, resulting in an expansion of tumor-reactive T cells to use for mutated peptide screening. Five patients were investigated, three of whom had a durable complete response (CR; 15+ years) in an autologous melanoma-pulsed dendritic cell clinical trial. We identified seven mutated antigens in total that stimulated T-effector memory cells in two of the five patients. While the procedure did not result in clinically applicable neoantigens for all patients, those identified were likely important in tumor clearance, leading to durable CR. The nature of the screening process allows results to be obtained rapidly and is easily applicable to a wide variety of different tumor types. Cancer Immunol Res; 3(9); 992–8. ©2015 AACR.
Original languageEnglish
Pages (from-to)992-998
Number of pages7
JournalCancer Immunology Research
Volume3
Issue number9
Early online date5 Jun 2015
DOIs
Publication statusPublished - Sep 2015

Cite this

Pritchard, A. L., Burel, J. G., Neller, M. A., Hayward, N. K., Lopez, J. A., Fatho, M., Lennerz, V., Woelfel, T., & Schmidt, C. W. (2015). Exome Sequencing to Predict Neoantigens in Melanoma. Cancer Immunology Research, 3(9), 992-998. https://doi.org/10.1158/2326-6066.CIR-15-0088