New Genomic Analysis Technology Has Been Used to Demonstrate How Cancer Drug Resistance Evolves

Personal Genome Diagnostics Inc. (PGDx), a leading provider of advanced cancer genome testing products and services, today announced that its ImmunoSELECT technology played a key role in a major new immuno-oncology (IO) study published in Cancer Discovery. The study demonstrated for the first time that acquired resistance to immune checkpoint inhibitor cancer drugs can develop as the landscape of somatic mutations evolves to remove the IO-targeted neoantigens.1 The study was conducted in the laboratory of PGDx co-founder Victor Velculescu, MD, PhD, who is Program Leader and Professor of Oncology at the Bloomberg~Kimmel Institute for Cancer Immunotherapy at Johns Hopkins University.

Mark Sausen, PGDx Vice President of Research & Development, commented, “Despite the increased efficacy and durability of treatment seen with IO therapies, some patients develop resistance to the therapy, and this study for the first time elucidates how this may result from the evolving cancer genome landscape. The comprehensive, multi-dimensional ImmunoSELECT approach revealed that in patients developing therapeutic resistance, somatic mutations specifically targeted by the IO therapy disappeared.”

PGDx’s ImmunoSELECT service identifies neoantigens--potentially immunogenic cancer mutations--to aid in the development of immuno-oncology therapies. Neoantigens are peptides containing tumor-specific mutations that may be capable of inducing an immune response to cancer. The exquisite tumor specificity of neoantigens makes them good targets for immunotherapy, but their identification requires highly accurate and comprehensive exome sequencing and tumor-specific mutation detection, as well as use of downstream approaches to further enrich and categorize the results. ImmunoSELECT combines the industry-leading accuracy of PGDx’s CancerXOMETM analysis with the company’s proprietary predictive bioinformatics pipeline specifically designed for immuno-oncology applications.

Dr. Sausen added, “These findings illustrate the value of ImmunoSELECT’s highly sensitive and specific approaches for whole-exome analyses and its multi-dimensional neoantigen prediction platform. The elucidation, discovery and validation of mutations that may be candidate neoantigens require a highly accurate mutation detection approach combined with integrated interpretation methods. ImmunoSELECT’s demonstrated ability to evaluate the effects of cancer therapy on the neoantigen landscape provides researchers with the detailed information they need to develop cancer immunotherapies and guide treatment options.”

ImmunoSELECT has the capability to detect somatic mutations with 95% sensitivity and 97% PPV for alterations with at least a 10% mutant allele frequency, and it has been validated using orthogonally available whole-exome Sanger sequencing data. The accuracy of ImmunoSELECT for detection of somatic alterations is strengthened by the use of tumor and patient-matched normal control DNA, ensuring exclusion of germline polymorphisms. The company also employs a proprietary strategy to stratify candidate neoantigens for experimental validation.