Single-Cell Proteomics: From Concept to Reality

Single-Cell Proteomics: From Concept to Reality

Single-cell functional proteomics is accelerating cancer immunology research and could improve clinical outcomes

Jing Zhou, MD, PhD

In the competitive world of cancer immunology, researchers are always searching for better ways to discover the cellular drivers of immune responses. Researchers have been dreaming about the ability to look at functional proteins from single cells for decades. The most urgent efforts in cancer immunology involve characterizing the complexity of tumor-immune interactions and include increasing tumor-antigen potency and modulating the host environment. These efforts are challenged by difficulty in detecting, understanding, and characterizing each immune cell’s function.

The current technologies used to analyze cell function can miss key information that can only be obtained by single-cell functional proteomics. For example, bulk cytokine analysis averages serum protein information from all cells and masks cytokine-driven cellular response differences between those that respond to the therapy and those that do not. Flow cytometry-based systems are often used to surface phenotype for many surface markers or to look at a few blocked cytokines within the cell, without detecting what’s truly being secreted from live single cells or identifying highly polyfunctional cell subsets that are associated with quality immune responses. To achieve the dream of complete cellular characterization, single-cell functional proteomics is needed to define the functional phenotype of each cell by the secreted, or extracellular, cytokines that dictate the response of each cell to the tumor. 

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Single-cell functional proteomics has uncovered unique correlative pre-clinical and clinical immune biomarkers, allowing researchers to differentiate mechanistic information in the competitive clinical world of immuno-oncology. In recent studies, single-cell functional biomarkers have revealed the cellular drivers of response in cancer immunology, gene edited cell therapies, and immune suppression from the host environment.

As the only functional cellular analysis tool with correlative biomarkers at single-cell resolution, IsoPlexis’ highly-multiplexed single-cell cytokine detection system has produced multiple correlative data sets in bispecifics, solid tumor checkpoint inhibitors, next generation cell therapies, and more. IsoPlexis’ IsoLight system is the only technology able to detect the range of functional extracellular proteins (30+ cytokines) per live single cell. This single-cell functional phenotyping technology is essential to researchers looking for complete characterization of cellular response. 

Many researchers and institutions are already using single-cell functional proteomics to help accelerate their cancer immunology programs by allowing them to make more informed decisions based on true cellular function. A recent commentary in the journal Blood concluded “by using single-cell analyses, heterogeneity may actually improve clinical outcomes.” 

Jing Zhou, MD, PhD

Jing Zhou, MD, PhD, is the chief scientific officer at IsoPlexis. She has led multiple studies with various biopharma and trial center leaders, particularly in the immuno-oncology space, to develop single-cell polyfunctional metrics that can distinguish and predict patient response to CAR-T and antibody-based cancer immunotherapies. Prior to IsoPlexis, she was an immunologist at the Yale School of Medicine with expertise in defining phenotype and functionality of immune cells in diseased and healthy settings, with 30+ scientific publications in leading journals. Jing earned her medical degree in clinical medicine from Bengbu Medical College, MS and PhD in immunology from Shanghai Jiao Tong University, and has been the principal investigator of NIH, AHA, and Yale University grants.

Published In:

May 2020

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