Assays May Help Researchers Discover Factors Underlying Immunotherapy Response

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A suite of assays that rely on a single instrument and its related software could help researchers identify factors that drive immunotherapy response.
A suite of assays that rely on a single instrument and its related software could help researchers identify factors that drive immunotherapy response.
The following article features coverage from the European Society for Medical Oncology (ESMO) 2018 meeting. Click here to read more of Cancer Therapy Advisor's conference coverage.

Novel platforms for the analysis of the tumor microenvironment, immune system, and driver mutations could drive oncology research to better understand the determinants of response to immunotherapy, according to a poster presented at the ESMO 2018 Congress in Munich, Germany.1

“These [immuno-oncology] panels provide sensitive, accurate, complementary information to further elucidate biological factors underlying response, resistance, and adverse events,” the authors wrote.

A subset of patients treated with immune checkpoint inhibitors or other immunotherapy approaches, such as chimeric antigen receptor T-cell (CAR-T) therapies, achieve a sustained complete response. What determines this response, however, is unknown. The aim of this study was to characterize a suite of assays that could be used in oncology research to drive a greater understanding of the tumor microenvironment, immune system, and driver mutations, all of which may be determinants of response.

This platform uses a single software program to allow joint interpretation of a suite of 3 different Oncomine assays. These assays use a single instrument, and each assay requires 20 ng of input material.

The first assays evaluated a 395-gene panel of genes involved in interferon and chemokine signaling, T- and B-cell activation, checkpoint pathways, antigen presentation, tumor proliferation, and expression markers of immune system effector cells to analyze patterns of gene expression. The study demonstrated that this assay has high sensitivity for detection, including detection of low-expressing genes that encode for interferon gamma.

The second assay sequenced the T-cell repertoire using total RNA harvested from blood to provide an estimate of T-cell diversity, among other properties. The sequencing is of the long-amplicon TCRB chain covering CDR1, CDR2, and CDR3.

The third assay is a 400-gene panel that evaluates tumor mutation load by analyzing somatic mutations per megabase using formalin-fixed paraffin-embedded tissue. This assay does not require a matched normal sample. The study demonstrated high reproducibility, concordance with matched normal tissue, correlation with exome mutation load, and accuracy on control cell lines.

The authors concluded that taken together, “These immuno-oncology 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.” 

Disclosure: The following study was funded by Thermo Fisher Scientific.

Read more of Cancer Therapy Advisor's coverage of the ESMO 2018 meeting by visiting the conference page.

Reference

  1. Hyland F, Looney T, Chaudhury R, Kamat A, Pankov A. Multi-dimensional immuno-oncology assays for understanding the immune system and tumor microenvironment. Presented at: the ESMO 2018 Congress; Munich, Germany: October 19-23, 2018. Abstract 137P.

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