Genetic Engineering & Biotechnology News

NOV1 2018

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GENengnews.com | Genetic Engineering & Biotechnology News | NOVEMBER 1, 2018 | 27 tein to the cell surface and a potentiator to make it work better. Data from Phase I and II studies demonstrated the potential to treat the underlying cause of CF in people who have one F508del mutation and one mini- mal function mutation not responsive to iva- caftor, tezacaftor, or the tezacaftor/ivacaftor combination, that is, in people who have a severe and difficult-to-treat type of the dis- ease," Dr. Van Goor says. All studies showed statistically significant improvements in lung function (ppFEV1) with a triple-combination regimen in these patients. "There are still patients for whom we will use biomarkers, for example, the F508L1 mutation," he notes. "In vitro assays can identify people without the F508del muta- tion on either allele that could respond." Clues within Isolated Immune Cells GEN spoke with David Messina, Ph.D., COO of Cofactor Genomics, who partici- pated in the panel discussion, "Building the Best Biomarker Driven Precision Medicine Clinical Trials." Founded by three former Human Ge- nome Project scientists, Cofactor has built a proprietary platform, its ImmunoPrism as- say, that the company says overcomes the chemical and computational challenges of performing complex immune profiling on clinical-grade human samples. The platform, comprising targeted molecular reagents and machine-learning software, accommodates samples from FFPE, FNA, and CNB archives as well as samples with very low sample in- puts, and it provides extensive immune char- acterization beyond current technologies— including differentiating cells such as M1 and M2 macrophages and regulatory T cells. Dr. Messina says that RNA analysis pro- vides the key to figuring out exactly what im- mune cells are present in a patient's tumor, potentially using the information to help pre- dict a patient's response to immunotherapy. "One of the critical factors in using novel immunotherapies such as checkpoint inhibi- tors is understanding how the immune sys- tem interacts with the tumor in the micro- environment. The amounts and ratios of im- mune cells can determine whether a patient will respond to a drug," says Dr. Messina. For example, he cites findings that show that the use of CD8 + /CD4 + TILs ratios in tumor biopsies may predict response to anti-PD1 treatment in metastatic melanoma and non- small cell lung cancer. "By isolating the pure immune cell sub- types and analyzing their RNA individu- ally, we've been able to develop a multidi- mensional gene expression model for what makes each immune cell unique, and getting a real-time readout of what's going on in the cell," he continues. "It's not possible with current technology to effectively assay every protein or cell surface marker, but we can quantify immune cells in tremendous detail using RNA. "We are profiling the immune content of the tumor with high sensitivity and we re- quire very little tumor material. We process it and return a fully analyzed report on each in- dividual sample—the assay profiles multiple immune cell types in a tumor sample simulta- neously. This enables a better understanding of response to therapies, disease progression, mechanism of action, and what combination of immunotherapies might make sense for a patient." "A patient sample contains a mixture of multiple cell types—we compare the material from the sample to what we have in our cu- rated database and can identify the mixture components—say 20% T cells or 5% regula- tory T cells," Dr. Messina details. "This level of resolution has previously not been pos- sible. We can compare the relative amounts of immune cell types within the sample. This is very important where the ratio of immune cells is key to understanding of the patient response to immunotherapies." "Success of immunotherapies has led to great efforts to identify new therapies of this class, and we see hundreds of immunothera- pies in development," he notes. "While it is exciting to think about the expansion of these therapies, we know that some of the biomarkers in use today are not sufficiently predictive of patient responses." "We believe our RNA-based assays can produce much more refined and predictive information about potential patient respons- es," he asserts. "We are eager to demonstrate this in a clinical setting." Reference 1. Rowe, SM, Verkman AS. Cystic fibrosis transmem- brane regulator correctors and potentiators. Cold Spring Harb. Perspect. Med. 2013; 3(7): a009761. www.ncbi.nlm.nih.gov/pmc/articles/PMC3685879/ pdf/cshperspectmed-CYS-a009761.pdf First-class PCR results served with every run Applied Biosystems ™ thermal cyclers For Research Use Only. Not for use in diagnostic procedures. © 2018 Thermo Fisher Scientific Inc. All rights reserved. All trademarks are the property of Thermo Fisher Scientific and its subsidiaries unless otherwise specified. COL07855 1018 Press the call button at thermofisher.com/thermalcyclerdemo • Trusted for reliability and precision for over 30 years • Verified for superior temperature accuracy and uniformity • Comprehensive portfolio of instruments delivering first-class PCR results for every application Find out more about Invitrogen ™ PCR reagents at thermofisher.com/amplifly Translational Medicine

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