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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22 Clinical OMICs March/April 2017 www.clinicalomics.com to inefficient isolation and sequencing techniques, neoanti- gens were "shelved" for more rapid and cost-effective ther- apeutic approaches . To truly appreciate the important role genomics plays in identifying key DNA alternations, a brief overview of how the immune system addresses antigens is necessary . T cells obtain their "education" within the thymus gland and, through a process called negative selection, are pre- vented from recognizing autoantigens, which most often includes tumor antigens . However, since tumors develop new genetic mutations that are not present in the thymus, the neoepitope-specific T-cell repertoire is not affected by the negative selection process . Moreover, since tumors are not homogenous in their mutational profile, i.e., various cells develop new mutations within the tumor often mak- ing them genotypically distinct from their neighbor, one tumor could contain thousands of potential neoantigens for the immune system to target . Finally, as mutated anti- gens are only expressed on cancer cells, T cells specific to these targets should not have negative effects on healthy tissue—thus rendering the mutated antigens ideal targets for therapeutic vaccination . As a result of the exponential decline in sequenc- ing costs and the concomitant rise in advanced NGS technologies, identification of tumor neoantigens has not only become a practical option, but a highly sought after personalized medicine approach . Clinical evidence in mouse models of cancer using neoantigen targeting strat- egies has shown this approach to be extremely efficacious and provides the appropriate proof of concept validation for NGS- identified tumor antigens as a potential precision (continued from previous page) As a result of the exponential decline in sequencing costs and the concomitant rise in advanced NGS technologies, identification of tumor neoantigens has not only become a practical option, but a highly sought-after personalized medicine approach. Cancer Immunotherapy: A pseudo-colored scanning electron micrograph of an oral squamous cancer cell (white) being attacked by two cytotoxic T cells (red), part of a natural immune response. Nanomedicine researchers are creating personalized cancer vaccines by loading neoantigens identified from the patient's tumor into nanoparticles. When presented with immune stimulants, the patient's own immune system is activated, leading to expansion of tumor- specific cytotoxic T cells. Rita Elena Serda, Duncan Comprehensive Cancer Center at Baylor College of Medicine, NCI, NIH (continued on page 24)

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