With a single-cell proteomics, identifying risk factors for long COVID

With a single-cell proteomics, identifying risk factors for long COVID ...

Proteomodynamics for single-cell propulsion are widely used by researchers to understand the complex roles of immune cells, specifically multi-functional cells. In a recent study, scientists aimed to investigate the dangers behind long COVID.

Sean Mackay, the CEO and co-founder of IsoPlexis, to discuss the platform and how single-cell functional proteomics is transforming our perception of health and disease.

Katie Brighton (KB): What are single-cell proteomics strategies advancing the understanding of complex diseases?

Sean Mackay (SM): As a result of the advancement of precision medicine, treatment options are becoming more tailored to each specific patient''s individual needs. These personalized medicines rely on advanced technology that improve the resolution and access to in vivo biology to create lasting, curative effects on health.

Researchers are missing critical functional information at a protein level without using genomic and surface marker analysis alone. Traditional bulk methods average across all cells, but critical cellular attributes are crucial to understanding response in patients.

Functional proteomics of one cell shows the functional cellular properties that are critical for regulating immune responses, thus allowing researchers to gain deep insights into the cells that are conducting responses in our bodies. Basically, a better understanding of immune cell function can benefit the understanding and treatment of a wide variety of diseases.

What separates the IsoPlexis approach from other single-cell technologies? Anna MacDonald (AM)

SM: As part of our research, we are investigating the immune system to uncover unique immune biomarkers in small subsets of highly polyfunctional cells, which we call superhero cells. Polyfunctionality is a powerful mediator of an individual''s ability to respond to treatment, and is known to be capable of persistence and long-term response.

In this way, we can adapt immunotherapies and targeted therapies to the cell behavior level so that they are more precise and personalized.

AM: Can you provide additional information on the Functional Cell Library, how it was developed, and what are superhero and supervillain cells, and what exactly are they identified?

The Functional Cell Library is a industry-leading mapping of highly functional, proteomically driven cells, uniquely identified by the IsoPlexis platform, that can determine how the human body responds to complex diseases and therapies.

These cells may be superhero cells (highly polyfunctional cells predictive of potency, patient response, survival, etc.) or supervillain cells (highly polyfunctional cells predictive of inflammation, toxicity, disease progression, etc.)

In a wide spectrum of high impact journals, the library categorizes how these cells have been used to predict cell product functional attributes and vaccine effectiveness, predict and monitor patient response to therapies.

The Functional Cell Library provides an unparalleled layer of proteomic analysis on a wide range of superpowered immune and tumor cell types that IsoPlexis has uniquely identified. For preclinical, translational, and clinical applications, the Functional Cell Library provides the bridge to leverage unique functional phenotyping patterns.

It is a valuable resource for oncology, immunology, neuroscience, autoimmune disorders, infectious disease, and cell and gene therapies, as well as targeted therapies, and others. It is now available as a industry-wide, literature-referenced, and consistently updated resource to leverage unique functional phenotyping data across a variety of cell types for product manufacturing and quality control, as well as preclinical, translational, and clinical applications.

Koko: What were the primary findings?

SM: In the study titled "Multiple Early Factors Anticipate Post-Acute COVID-19 Sequelae," researchers compared patient symptoms with extensive testing of blood-based biomarkers throughout COVID-19 infection to identify factors associated with the development of post-Acute sequelae of COVID-19 (PASC). PASC is the technical term for long-term COVID, resulting in a wide variety of new, returning or ongoing health problems that individuals may encounter four or more weeks

309 patients were monitored from their initial clinical diagnosis to their early-stage recovery from acute disease, spanning until 23 months post-diagnostic to identify the early signs that influence long COVID, including the increase in the number of supervillain immune cell subsets.

Can you please tell us about the IsoPlexis single-cell functional proteomics platform? How did it help to identify different immune cell types and inflammation in long-term COVID?

SM: The IsoPlexis single-cell proteomics provided a unique tool to analyze the functional effects of different cell types across several parameters, and the interactions between adaptive and innate immune responses that contributed to effector functions or inflammation in long COVID.

Proteomics from IsoPlexis revealed a correlation between the increased frequency of supervillain T cell subsets with type 1, type 2, and intermediate polarized PASC endotypes and disease severity in convalescence. Moreover, single-cell functional observations reveal the supervillain monocytes in convalescent patients compared to healthy individuals that correlated with all four identifiable endotypes of PASC, indicating the effect of monocytes on a sustained inflammation at convalescence.

Now, the research has identified four endotypes of COVID-19 after-acute sequelae, so how could this information be used to shape treatment strategies?

SM: Through understanding the supervillain cells that drive inflammation in diseases like COVID-19, we can apply these learnings to a broad range of critical challenges for inflammatory diseases, such as information on disease progression and the identification of potential therapies. Our platform has previously been used for development of vaccines, as well as understanding the mechanisms of transplant rejection, cytokine release syndrome, and toxicity, and autoimmune inflammation.

What other disease and application areas might benefit from single-cell functional proteomics, outside of COVID-19?

SM: Our single-cell functional proteomics is vital for immune monitoring and immune health. In several studies, our functional single-cell analysis was conducted to demonstrate patient attributes in research areas such as cancer immunology, cell therapy, and autoimmune inflammation.

Two recent Nature Medicine papers highlight the unique significance of IsoPlexis'' unique-cell prognosis for the performance of new cell therapies, including the chimeric antigen receptor (CAR) T-cells in blood cancer and tumor-infiltrating lymphocytes (TILs) in vitro. One of the greatest obstacles in improving cell therapies is discovering exactly how these living immune therapies work as early as possible. Through these two high-impact publications, researchers developed the technique to gain better understanding of how C

In a Phase 2 clinical study for combination checkpoint and novel IL-2 agonist therapy, our platform identified a blood-based biomarker that correlated with patient response and progression-free survival.

What else would you like to mention in the comments?

Duomic, which has now been created, is ideal for researchers to develop both functional proteomics and gene expression from a single cell. This allows researchers to investigate the genetic potentials of these super cells, and has a variety of applications:

  • Revealing the genetic drivers of CAR T cells to create more potent and durable next-generation therapeutics
  • Profiling the TCR repertoire, accelerating the understanding of the immune system and ability to develop new therapeutics
  • Recoding gene and gene pathways driving therapeutic resistance and tumor progression

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