On January 25, 2022 LUMICKS, a next generation life science tools company, reported that research findings from a consortium, led by researchers at Cancer Center Amsterdam, Amsterdam University Medical Centers, published in Science Translational Medicine, detailed a novel design strategy for preventing tumor escape through improved chimeric antigen receptor (CAR) T cell therapy for common blood cancers (Press release, LUMICKS, JAN 25, 2022, View Source;utm_medium=rss&utm_campaign=new-study-published-by-group-of-maria-themeli-cell-aviditys-power-as-a-functional-biomarker-for-improved-car-t-design-in-preventing-tumor-relapse [SID1234606761]).
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Using both cell avidity measurements, as provided by LUMICKS’ z-Movi Cell Avidity Analyzer, and traditional immuno-assays, the researchers successfully demonstrated that co-expression of costimulatory receptors (CCR) along with an FDA approved BCMA and CD19 CAR can improve both durability of potential treatments as well as sensitivity to recognize and lyse various variants of multiple myeloma and acute lymphoblastic leukemia with low antigen density. This innovative dual-targeting approach provides an exciting new avenue for next-generation therapies that may overcome many common problems of current approved therapies, including high rates of relapse. The study was published in the December 2021 issue of Science Translational Medicine.
In the study profiled, the researchers set out to characterize the dual targeting system through co-expression of high-affinity engagement of co-stimulatory molecules with a BCMA CAR. Using LUMICKS’ z-Movi Analyzer, the researchers were able to determine that dual targeting with CD38-binding CCR enhanced the cytotoxicity of BCMA-CAR-T cells by increasing their binding avidity. This increasing activity improved the overall sensitivity of these cells as compared to other approved therapies. The measurement of cell avidity’s power as a functional biomarker provided strong support for the mechanism of action underlying these results and a rational basis for ongoing efforts to improve next-generation CARs for enhanced therapeutic efficacy.
"The z-Movi platform’s distinct ability to measure and quantify avidity provides a powerful tool for immuno-oncologists," said Maria Themeli, M.D., Ph.D. Assistant Professor at Amsterdam UMC and corresponding author of the study. "The instrument provided an essential piece of evidence in our investigation, giving us critical insight into how these engineered cells work and what is ultimately responsible for their changes in behavior with this new dual-targeting strategy. Understanding mechanism of action is fundamentally important for any effective drug development study."
The LUMICKS z-Movi platform provides the unique ability to measure the avidity of hundreds of cells in parallel using an intuitive and convenient workflow based on the application of acoustic force. The strength of interaction between single targeting (first generation) and double-targeting T cells and MM1.S target cells was measured in the study. Statistically robust differences in avidity were measured between the two CAR designs, demonstrating the underlying cause of the enhanced cytotoxicity of the dual targeting system.
"This innovative new work, highlighting LUMICKS’ z-Movi as a critical tool to enable CAR-T developers to precisely understand fundamental principles of therapy design, is both exciting and important," said Andrea Candelli, Ph.D., Chief Scientific Officer and co-founder of LUMICKS. "This is the first step in our mission to demonstrate and validate the power of cell avidity as the biomarker for immuno-oncology research and development."