2018 AACR: Supporting Neoantigen Discovery and Monitoring in Plasma Through Analytical Validation of a Deep Augmented Content Enhanced (ACE) Exome
Neoantigens are increasingly critical in immuno-oncology as a therapeutic target for neoantigen-based personalized cancer vaccines and as a potential biomarker for immunotherapy response. An important step in identifying neoantigens is comprehensive exome and transcriptome sequencing of a tumor biopsy sample and the matched normal to enable identication of putative neoantigens derived from mutations in any gene in the genome.
However, as tumor biopsy samples cannot always be obtained, and because tumor heterogeneity can result in an incomplete set of neoantigens from a single biopsy, we developed our Accuracy and Content
Enhanced (ACE) circulating tumor DNA (ctDNA) Exome to (1) identify neoantigens in cell free DNA (cfDNA) as a complement to tumor biopsy derived neoantigens and (2) track neoantigens in the cfDNA post immuno-therapy treatment. Our ACE ctDNA Exome covers ~ 20,000 genes as neoantigens can occur in any gene across the genome. This is in contrast to most current tumor cfDNA tests which are designed to assess a small number of variants or genes (often <100), and as such will miss many putative neoantigens. Our ACE ctDNA Exome is performed at very high sequencing depth to accurately identify lower allele frequency variants that are candidate neoantigens.
Here we want to assess the limit of detection (LOD) of our ACE ctDNA Exome assay for small nucleotide variants (SNV) and demonstrate the utility of the assay for both monitoring and de-novo identication of neoantigens directly from cfDNA.