Clinical OMICS

MAR-APR 2017

Healthcare magazine for research scientists, labs, pathologists, hospitals, cancer centers, physicians and biopharma companies providing news articles, expert interviews and videos about molecular diagnostics in precision medicine

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Page 25 of 47

24 Clinical OMICs March/April 2017 medicine tool . Innovations to single cell sequencing meth- odologies have allowed investigators to identify neoantigen markers from heterogenous tumor tissues . Additionally, the use of in silico epitope prediction algorithms is moving a once labor-intensive process to one that could see routine clinical use as a diagnostic tool . "We are working on improving the accuracy of neoanti- gen prediction because it can ultimately improve the effi- cacy of vaccines synthesized based on those neoantigens, or any diagnostics that use it as a predictive biomarker," Dr. Chen noted . "To improve neoantigen predictions, we are innovating on sequencing, informatics, machine learning, and validation strategies." Roadblocks Destined to Be Cleared Integral as genomics has been for recent advances in immu- notherapy, the merger of these two heady approaches comes with its own set of challenges . For instance, computational approaches for analyzing sequencing data as well as epi- tope identification, have not evolved as rapidly as sequenc- ing technology—ultimately creating an information logjam that considerably slows down the research and development pipeline . To their credit, bioinformatists have been up to the task of unjamming the chute by developing new software that has made neoantigen identification a less labor intensive, and even approachable, process for potential routine clinical use . Moreover, since a patient's HLA type can be extracted from NGS information with high accuracy, that data can now be analyzed with new software to enable epitope prediction of candidate antigens for drug or cancer vaccine development . "Developing robust and reproducible technologies that are easy to use, automatable, reproducible, and produce consistent results across labs and operators is critical," Hyland stated. "Assays need to be affordable, with avail- able easy-to-use analysis tools, and interpretable results." Hyland's statement touches on two critical points that are often taken for granted in the research realm: reproducibil- ity and sample size . When performing in vitro experiments at the bench, it's fairly simple to work in replicate samples in order to get a hold on sample error rates and experimen- tal variance . However, when attempting to translate basic research findings to clinically useful data, experimental parameters are a significant detail, as replicate numbers of humans are a limiting factor, to say the least . "Oncology is a rapidly evolving space creating challenges for clinicians, and researchers to keep up with the pace of discovery." Dr. Leite remarked. "As in any new branch of clinical investigation, processing enough samples to gen- erate statistically significant trends while managing the myriad of confounding clinical variables will always be the main challenges." (continued from page 22) Exome sequencing provides clinicians a rapid genomic snapshot of gene expres- sion at the time the genetic material is isolated. This technique is especially use- ful for identifying underlying gene muta- tions and diagnosing the genetic causes of disease. Since its first diagnostic use within a clinical setting in 2011, advances and modifications to exome sequencing have enabled the technique to become a sensitive enough and proven tool for more routine clinical usage. Companies like Personalis have spent a substantial amount of their time and resources toward developing improved exome sequencing methodologies that can now be applied to immuno-on- cology efforts. The Accuracy and Con- tent Enhanced—or ACE—platform can provide more comprehensive exome sequencing coverage of more than 8,000 genes with known medical importance. "Our ACE ImmunoID platform, by elu- cidating the "Immunogram," is technol- ogy available now that can really move research forward, especially in transla- tional and precision medicine," explained Richard Chen, M.D., chief scientific officer at Personalis. "The next step is deploying this type of technology in large-scale studies where outcomes and clinical response to immunotherapy are known. From these kinds of studies new biomarkers for response, mechanisms for tumor escape, and insights into the immunogenicity of neoantigens can be drawn—really getting at the underlying mechanisms for immune response." Dr. Chen told Clinical OMICs that the ACE ImmunoID platform was ideal to characterize the genetics of tumors and tumor antigens comprehensively. "We and our partners are already using infor- mation like this to power therapeutics such as personalized neoantigen-based cancer vaccines, and we believe it will also become central to the next gener- ation of immunotherapy diagnostics." n Immuno-Oncology's ACE in the Hole xubingruo / Getty Images

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