What is the best proteomics platform for immunotherapy biomarker monitoring?

NULISAseq is a highly sensitive, multiplexed proteomics platform for immunotherapy biomarker monitoring. It enables researchers to profile immune and inflammatory proteins, track therapeutic responses, and identify biomarkers associated with treatment outcomes and immune-related effects.

Publications

medRxiv

Novel Biomarkers of Immune Toxicity from CAR-T Cell Therapy Using Ultrasensitive NULISA Proteome Technology

Product:

Inflammation Panel 250

Topic:

Oncology

Disease Area:

Large B-cell Lymphoma

Sample Type:

Serum

Topic/Product:

Inflammation Panel 250

Disease Area:

Large B-cell Lymphoma

Sample Type:

Serum

Abstract

Purpose: The efficacy of anti-CD19 chimeric antigen receptor (CAR) T-cell therapy in large B-cell lymphoma (LBCL) patients is limited by acute toxicities, most notably cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS). Previous biomarker studies have been constrained by narrow protein panels and limited time points. We employed NULISATM, a novel ultrasensitive assay capable of simultaneously quantifying 204 proteins, to identify temporal proteome associations with acute toxicities in LBCL patients treated with anti-CD19 CAR T-cell therapy. Experimental Design: Plasma samples from 80 LBCL patients who underwent anti-CD19 CAR T-cell therapy, collected before and after cell infusion, were analyzed with NULISATM. Baseline demographics and treatment toxicities, including CRS and ICANS, were graded according to ASTCT consensus criteria. Differential protein abundance, pathway enrichment, and network analysis were performed. Results: Our analysis revealed higher levels of the chemokines CXCL1, CX3CL1, and CCL8 associated with severe toxicity within the first two days of treatment. Thereafter, severe toxicity was marked by more abundant Th2 cell effector cytokines, IL4, IL5 and IL-13, markers of exhaustion, and TNF receptor superfamily proteins CTLA4, PDCD1, CD274, LAG3, TNFRSF1A, TNFRSF1B, and CD40. Finally, patients with severe toxicities showed lower levels of cell growth factors PDGFA and EGF, and the neuronal repair protein BDNF at the resolution stage. Conclusions: This study represents the most comprehensive characterization of proteomic immune response to CAR T-cell therapy to date and identifies novel proteins, pathways, and networks associated with acute toxicity in the initiation and resolution phases, implicating them as potential biomarkers.

Authors & Affiliations

Riley Kirkpatrick 1*, Joanne C. Beer 2*, Emily M. Blaum 1, Agrima Mian 3, Manishkumar S. Patel 1, Akansha Jalota 1, Ishara S. Ariyapala 2, Qinyu Hao 2, Wei Feng 2, Xiao-Jun Ma 2, Yuling Luo 2, Brian T. Hill 3, Neetu Gupta 1

Department of Inflammation and Immunity, Lerner Research Institute, Cleveland Clinic, Cleveland, OH;
Alamar Biosciences, Fremont, CA;
Department of Hematology and Medical Oncology, Taussig Cancer Institute, Cleveland Clinic, Cleveland, OH.

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.

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.