The ability to use circulating peripheral blood cells and matched tumour sequencing data as a basis for neoantigen prediction has exciting possibilities for application in the personalised treatment of cancer patients. We have used a high throughput screening approach, combining whole-exome sequence data, mRNA microarrays and publically available epitope prediction algorithm output to identify mutated proteins processed and displayed by patient tumours and recognised by circulating immune cells. Matched autologous melanoma cell lines and peripheral blood mononuclear cells were used to create mixed lymphocyte tumour cell cultures (MLTC), resulting in an expansion of tumour-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 out of the five patients. While the procedure did not result in clinically applicable neoantigens for all patients, those identified were likely important in tumour 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 tumour types.
- Received April 2, 2015.
- Revision received May 21, 2015.
- Accepted May 21, 2015.
- Copyright © 2015, American Association for Cancer Research.