A novel immunogenomics platform that can characterize the tumor and tumor microenvironment (TME) from a single formalin-fixed paraffin embedded (FFPE) patient sample was shown to produce results that were comparable to current techniques. The study was recently reported at the AACR-NCI-EORTC International Conference on Molecular Targets and Cancer Therapeutics.
Immunogenomic profiling of the tumor and the tumor microenvironment is “critical” to identify new biomarkers of immunotherapy response and understanding resistance, the study authors, from the company Personalis, Inc., explained. “However, running a comprehensive array of biomarker assays for each patient sample is often impractical given limited sample quantity, processing complexity, and prohibitive cost.”
The study researchers developed an augmented exome and transcriptome-based platform and designed it in such as way detect somatic single nucleotide variants, insertions and deletions, copy-number alterations, and fusions across approximately 20,000 genes and to determine expression signatures, human leukocyte antigen (HLA) typing and loss of heterozygosity, T-cell receptor (TCR)/B-cell receptor repertoires, oncoviruses, tumor-infiltrating lymphocytes, clinically actionable mutations, tumor mutational burden (TMB), and microsatellite instability (MSI) status.
With 50 ng of DNA per FFPE sample and coextracted RNA, the platform was able to evaluate 17% to 40% more genes than in a nonaugmented exome. The platform also showed concordance for TCR alpha and beta clonotype profiling compared with a targeted TCR kit (R2>0.9 and >0.94) and concordance for development of immune cell signatures compared with synthetic and mass cytometry-derived validation sets.
In addition, the platform showed high accuracy for HLA Class I (99.1%) HLA Class II (95%) typing, ability to detect several oncoviruses, and accurate determination of TMB and MSI status. The platform also showed a high sensitivity and specificity for clinically reportable mutations.
“We have developed a novel immunogenomics platform that can characterize both the tumor and TME from a single sample,” the study authors wrote in the abstract.
Power R, Bartha G, Harris J, et al. A comprehensive, highly accurate genomics platform for precision immunotherapy: Simultaneously characterize tumors and the TME from a single FFPE sample. Presented at: AACR-NCI-EORTC International Conference on Molecular Targets and Cancer Therapeutics; October 26–30, 2019: Boston, Massachusetts. Abstract A051.