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Comprehensive Characterization of Inflammatory Cytokines in Chronic Lymphocytic Leukemia Highlight Immune Dysregulation and Associates with MRD

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  • December 27, 2024
Topic/Product:
Oncology
Disease Area:
Sample Type:

Background

Chronic lymphocytic leukemia (CLL) is characterized by immune dysfunction and dysregulation resulting in increased risk for infection and second cancers. Prior studies indicated that chronic inflammation may contribute to worse clinical course in CLL. Comprehensive assessment of the inflammatory mediators and in context of response to treatment, particularly measurable residual disease (MRD), remains unexplored. We aimed to leverage a novel proteomic profiling of >250 inflammatory proteins with high sensitivity assay to assess serum inflammatory profiles at baseline and post-treatment and associations with MRD status.

Sample and Methods

— Baseline samples of 64 CLL patients treated first-line therapy on the randomized trial of acalabrutinib (ACA) + venetoclax (VEN) +/- early obinutuzumab (OBIN) (NCT04169737)
— 18 patients with a paired end of treatment (EOC26) sample with bone marrow (BM) undetectable MRD status (uMRD4; 10-4 sensitivity)
— 26 healthy donor plasma samples as control
— Inflammatory proteome was evaluated through blood-based proteomic profiling of 251 soluble inflammatory proteins using NUcleic acid Linked Immuno-Sandwich Assay (NULISA), a proximity-ligation assay based on NGS or PCR allowing attomolar (10-18) detection
— Comparative analysis to identify differentially expressed cytokines at baseline or EOC26 compared to healthy to define dysregulated inflammatory protein networks
— Logistic regression to assess cytokines prognostic for early uMRD4 at EOC9

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Authors & Affiliations

Bofei Wang PhD, Jessica Root MS, Isabella Garza BS, Joyce Breaker BS, William Wierda MD, PhD, Hussein A. Abbas MD, PhD, Patrick K. Reville MD, MPH

Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.

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Steve Williams, MD, PhD

CSO

Dr. Willams serves as the company’s Chief Scientific Officer. He was previously Chief Medical Officer at Standard Biotools and at SomaLogic where he pioneered the discipline for discovery and validation of predictive, diagnostic and prognostic models using machine-learning applied to large-plex proteomics. 20 such tests were used for drug characterization, safety and efficacy when incorporated in clinical drug trials at Pharma/Biotech and 17 different multivariate tests were validated and translated into regulated healthcare uses. Prior to SomaLogic, Dr. Williams was at Pfizer in the UK and the USA as a clinical triallist in Translational Medicine, and subsequently as VP, Global Clinical Technology. He sat on the National Advisory Council for the National Institute of Biomedical Imaging and Bioengineering, the Executive Committee for the FNIH Biomarkers Consortium, and worked with FDA and PhRMA on developing evidentiary standards for biomarker qualification. Dr. William’s medical training was in London, at Charing Cross and Westminster Medical School, followed by a PhD in medicine/physiology at the same institution and training in Radiology at the University of Newcastle Upon Tyne. Steve is co-inventor on 26 proteomics patents and author/coauthor on multiple foundational proteomics manuscripts.

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Justin McAnear

CFO

Mr. McAnear serves as the company’s Chief Financial Officer. He brings over 25 years of operational and financial leadership experience across various sectors and was instrumental in taking 10x Genomics public in 2019, serving as its CFO for over five years. Mr. McAnear served for over 3 years as Tesla’s VP of Worldwide Finance and Operations, supporting landmark initiatives such as the Model X and Model 3 launches and Solar City acquisition.  He also held various roles at Apple and J&J earlier in his career and served as a naval officer and aviator for over 9 years.