Caris Life Sciences Identifies a Splicing Complex on the Surface of Non-Hodgkin's Lymphoma Cells that Is a Potential Anti-Tumor Drug Target

Findings from Caris Life Sciences and University of Bonn, published in Cell Chemical Biology, demonstrate for the first time a spliceosomal complex identified on surface of cancer cells

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Caris Life Sciences

Mar 28, 2019, 11:00 ET

IRVING, Texas, March 28, 2019 /PRNewswire/ -- Caris Life Sciences®, a leading innovator in molecular science focused on fulfilling the promise of precision medicine, today announced the publication of new data in Cell Chemical Biology that may offer a novel pathway to treat Non-Hodgkin's lymphoma (NHL). The published findings show for the first time the identification of a spliceosomal complex on the surface of cancer cells that have potential as a unique anti-tumor drug target.

The paper, "Translocation of a cell surface spliceosomal complex induces alternative splicing events and lymphoma cell necrosis," confirms the identification of a molecular spliceosomal complex, comprised of proteins typically found in the nucleus or cytoplasm of cells, that is unexpectedly localized to the surface of the cancer cell.

The complex was discovered using an NHL-specific single-stranded DNA aptamer, C10.36. The aptamer was discovered by Caris Life Sciences collaborators Günter Mayer and Michael Famulok at the Life & Medical Sciences Institute at University of Bonn. Target identification was performed using Caris' proprietary ADAPT Biotargeting System™ previously described by Domenyuk et al. in Scientific Reports and Nature Communications.

The results show that when the C10.36 aptamer binds to its target on the cell surface, the complex is translocated into the cell causing global changes in RNA splicing ("splicing chaos") and necrotic cell death. This represents the first time a spliceosomal complex has been identified on the cell surface.

"To our knowledge, this study demonstrates that the C10.36 aptamer specifically recognizes a unique spatial arrangement of a large spliceosomal complex on the surface of NHL cells," said Heather A. O'Neill, Ph.D., Senior Research Scientist at Caris Life Sciences and co-lead author of the paper. "We believe that the mis-localization of the complex on the surface of the cell may play a role in driving and/or maintaining the malignant state. For the first time, we have identified a spliceosomal complex on the surface of cancer cells that may be pursued as a novel drug target."

"The ability of the aptamer to cause cell necrosis and the presence of the complex on various NHL cells opens two interesting paths of further fundamental and translational research. On the one hand, our findings motivate studies to unravel the biological function of the surface spliceosomal complexes and its role in cancer, but also to investigate the aptamer's potential as a therapeutic agent," said Günter Mayer, Ph.D., Center of Aptamer Research and Development, University of Bonn.

"This paper further demonstrates the power of our proprietary ADAPT Biotargeting System™, which is capable of identifying novel drug targets for therapeutic and diagnostic applications," said David Spetzler, M.S., Ph.D., M.B.A., President and Chief Scientific Officer of Caris Life Sciences. "Our work with the University of Bonn is a prime example of how our use of ADAPT can assist researchers by identifying unique molecular targets for deeper understanding and exploring new approaches to cancer therapy."

The ADAPT Biotargeting System™ is Caris' proprietary unbiased profiling platform that uses a broad library of synthetically-manufactured molecules (aptamers) that bind to a wide range of biological targets and characterize complex biological systems in their native state, enabling them to profile biological samples at a systems-wide scale.

The paper was published in the March 28 online issue of Cell Chemical Biology and is available online here and DOI: https://doi.org/10.1016/j.chembiol.2019.02.016.

About Caris Life Sciences
Caris Life Sciences® is a leading innovator in molecular science focused on fulfilling the promise of precision medicine through quality and innovation. The company's suite of market-leading molecular profiling offerings assess DNA, RNA and proteins to reveal a molecular blueprint that helps physicians and cancer patients make more precise and personalized treatment decisions. Caris is also advancing precision medicine with Next Generation Profiling™ that combines its innovative service offerings, Caris Molecular Intelligence® and ADAPT Biotargeting System™, with its proprietary artificial intelligence analytics engine, DEAN™, to analyze the whole exome, whole transcriptome and complete cancer proteome. This information, coupled with mature clinical outcomes on thousands of patients, provides unmatched molecular solutions for patients, physicians, payers and biopharmaceutical organizations. Headquartered in Irving, Texas, Caris Life Sciences offers services throughout the U.S., Europe, Asia and other international markets. To learn more, please visit www.CarisLifeSciences.com or follow us on Twitter (@CarisLS).

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