With the use of single-cell proteomics, identifying risk factors for long COVID

With the use of single-cell proteomics, identifying risk factors for long COVID ...

Researchers have analyzed the molecular properties of cell function using IsoPlexis technologies for single-cell proteomics to understand the complex roles of immune cells, particularly multi-functional cells. In a recent study, the company''s platform was employed by researchers attempting to identify the dangers behind long COVID.

Sean Mackay, the CEO and co-founder of IsoPlexis, was caught up with to learn more about the platform and how single-cell functional proteomics is contributing to our understanding of health and disease.

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

Sean Mackay (SM): With the advancement of precision medicine, treatment options are becoming more tailored to each individual individual patient''s needs. These personalized medicines rely on advanced technologies that improve patient resolution and access to in-vivo biology to have long-term therapeutic effects.

Researchers are missing critical functional information at a protein level with genomic and surface marker analysis alone. Traditional bulk methods average across all cells, losing critical physiological attributes.

Proteomodynamics in one-cell clinical trials uncovering functional cell attributes that are crucial in regulating immune responses, allowing researchers to gain insights into cells that are regulating responses in our bodies. Basically, a better understanding of immune cell function can assist the diagnosis and treatment of a wide range of illnesses.

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

SM: As a result of our flow cytometry and unique monocell genomics, we are testing the immune system to reveal unique immune biomarkers in small subsets of highly polyfunctional cells, known as superhero cells. Polyfunctionality has been found to be beneficial to patients'' potential, persistence, and long-term response.

For the first time, with the IsoPlexis technology, we can now identify and predict how these superhero cells influence the immune response much earlier in the clinical process, by means of functional proteins (e.g., cytokines, chemokines, growth factors, etc.). In this manner, we may modify immunotherapies and targeted therapies at the cellular behavior level so that they are more precise and personalized.

AM: Do you know more about the Functional Cell Library and how it was developed? What are the superhero and supervillain cells, and how are they identified?

The Functional Cell Library is a industry-leading program to mapping highly functional, proteomically driven cells, uniquely identified by the IsoPlexis platform, that enables the human body to respond to complex illnesses 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, toxic, disease progression, etc.)

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

The Functional Cell Library provides the foundation for clinical, preclinical, and translational applications to utilize unique functional phenotyping algorithms to patient responses in vivo.

It is a valuable resource for oncology, immunology, neurology, autoimmune disorders, and infectious disease, as well as cell and gene therapies, 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 wide range of cell types for product manufacturing and quality control, as well as preclinical, translational, and clinical applications.

What were the greatest findings from the Cell study? KB: Can you give us an overview of the Cell study?

SM: In the paper titled "Multiple Early Factors Anticipate Post-Acute COVID-19 Sequelae," researchers correlated patient symptoms with in-depth profiling of blood-based biomarkers throughout COVID-19 infection to identify factors associated with the formation of post-acute sequelae of COVID-19 (PASC). This technique is used to describe long-term COVID, resulting in a range of new, returning, or ongoing health problems.

309 patients died after being diagnosed as a result of acute disease, ranging from initial clinical diagnosis to early-stage recovery, and searching for early signs that aid long-term COVID, notably the increased frequency of supervillain immune cell subsets.

Can you tell us how the IsoPlexis single-cell functional proteomics platform helped to identify the presence of different immune cell types and inflammation in long COVID?

SM: Proteomics for IsoPlexis single-cell interactions allowed for a unique insight to dissect the functional effects of different cell types across multiple timepoints, as well as the interplay between innate and adaptive immune responses that contributed to effector functions or inflammation in long COVID.

The IsoPlexis proteomics showed a correlation between the increasing frequency of supervillain T cell subsets with type 1, type 2 and intermediate polarized PASC endotypes and disease severity at convalescence. The single-cell functional analysis also showed the supervillain monocytes in convalescent patients that correlated with all four identifiable endotypes of PASC, indicating the effects of monocytes on an increased inflammation at convalescence.

KB: Now the study has identified four endotypes of COVID-19 post-acute sequelae, and how might 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 insights to a wide spectrum of critical challenges for inflammatory diseases, such as insights into disease progression, and the identification of suitable targets for treatment. Our platform has previously been used for the 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 can benefit from single-cell functional proteomics, outside of COVID-19?

SM: Our single-cell functional proteomics is essential for immune monitoring and immune health. In several studies, our functional single-cell analysis demonstrates patient attributes, particularly in cancer immunology, cell therapy, and others.

Two recent Nature Medicine papers demonstrate the unique capability of IsoPlexis'' unique-cell proteomic tool to understand the potential of novel cell therapies, including chimeric antigen receptors (CAR) T-cells in blood cancer and tumor-infiltrating lymphocytes. One of the greatest difficulties in improving cell therapies is understanding exactly how these living immune medications work as early as possible. This results in improved evaluations of quality, potentiality, and durability.

In a Phase 2 clinical trial 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.

Is there any other question you''d like to mention in the comments section?

Duomic, a revolutionary technology that allows researchers to detect both functional proteomics and gene expression from one cell, is available for free on request. This technology allows researchers to explore both functional proteomics and gene expression patterns from the same one cell.

  • 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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