Biomarker Development for Immuno-Oncology and Cancer immunotherapy: Simultaneous Digital Counting of Nucleic-Acids and Proteins at 800-Plex

Both the ENCODE and TCGA projects highlighted the value of quantifying multiple biomarker classes (DNA, RNA, and protein) from cancer tumor samples. In the case of cancer immunotherapy, the importance of measuring non-DNA markers (e.g., mRNA and proteins) becomes crucial since cell signaling, tumor microenvironment, and protein-protein interactions dominate over pure SNP-based (DNA) driver mutations in determining therapeutic response. Combining multiple data types together into a single correlated analysis, however, is adversely effected by the drastically different methodologies utilized for measurement. For example, the fluorescence signal intensity obtained from a camera imaging a protein array (e.g., RPPA) is very difficult to correlate directly with an RNA sequencing count of a clonally amplified, cDNA-converted, mRNA molecule. New developments in multiple biomarker-class optical barcode counting significantly reduce this problem. Recent developments using NanoString Technology has shown how optical barcode technology can be utilized for multiplexed digital counting of proteins and be combined with simultaneous digital counting of nucleic acids on a single platform.