Abstract 6106
Background
The promise of immuno-oncology (IO) is the potential for activating the immune system of an individual with cancer to destroy the tumor and metastases, and cause a complete and persistent response. A percentage of patients treated with checkpoint inhibitors or Car-T cell therapies exhibit complete response. However understanding all the determinants of response, and what combination of therapies can maximize efficacy and minimize adverse events, is still poorly understood. Further understanding the properties of the tumor micro-environment, the immune system, and driver mutations in the tumor provides the most comprehensive picture, enabling personalized oncology research.
Methods
We describe a suite of Oncomine assays that use a single chemistry and instrument with 20ng of input material each. The first measures patterns of gene expression of 395 genes that capture interferon and chemokine signaling, T and B cell activation, checkpoint pathway, antigen presentation, and tumor proliferation, measuring the expression of markers specific to different effector cell types. We demonstrate highly sensitive detection of low expressing genes including Interferon-Gamma. The second is the T-cell Repertoire sequencing assay. This assay uses total RNA from blood for long-amplicon TCRB chain sequencing, covering CDR1, 2 & 3. This assay provides an estimate of T cell diversity and other properties. The third is the Tumor Mutation Load assay. This 400-gene panel measures somatic mutations/Mb on FFPE samples, without requiring a matched normal. We demonstrated high reproducibility on FFPE, concordance with matched normal, correlation with exome mutation load, and accuracy on control cell lines.
Results
Together, these IO panels provide sensitive, accurate, complementary information to further elucidate biological factors underlying response, resistance, and adverse events. A single software for these diverse assays supports joint interpretation of this data.
Conclusions
These IO assays enable deep, broad, multidimensional characterization of biomarkers to explore predictors of response, optimal combination therapy, and avoidance of adverse events, accelerating research into immunotherapy for personalized oncology.
Clinical trial identification
Legal entity responsible for the study
Thermo Fisher Scientific.
Funding
Thermo Fisher Scientific.
Editorial Acknowledgement
Disclosure
F. Hyland, T. Looney, R. Chaudhury, A. Kamat, A. Pankov: Employee of Thermo Fisher Scientific.