Researchers aim to investigate the molecular implications 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 survey, the company''s platform was used by researchers to identify the danger factors that sparked long COVID.
Sean Mackay, IsoPlexis'' CEO and co-founder, was interviewed to learn more about the platform and how single-cell functional proteomics is transforming our understanding of health and disease.
Katie Brighton (KB): How are single-cell proteomics approaches advancing the understanding of complex diseases?
Sean Mackay (SM): The advancement of precision medicine has prompted more patients to customize their specific needs. These personalized medicines rely on advanced technologies that provide a higher resolution and greater access to in vivo biology to help with lasting, curative effects.
Researchers are missing critical functional information at a protein level with genomic and surface marker analyses alone. Traditional bulk methods average across all cells, revealing that critical cellular attributes are essential to understanding response in patients.
Functional proteomics of a single-cell cell uncovers the functional cellular attributes that are critical for regulating immune responses, thus allowing researchers to gain deeper insight into cells that are inferred responses in our bodies. Ideally, a better understanding of immune cell function can benefit the understanding and treatment of a wide range of difficulties.
What differentiates the IsoPlexis approach from other single-cell technologies? Anna MacDonald (AM): What makes the difference between the two?
SM: As part of our research, we are investigating the immune system to uncover unique immune biomarkers in small groups of highly polyfunctional cells, which we call superhero cells. Polyfunctionality has been found to be beneficial to therapeutic potentials, such as potency, persistence, and long-term response in patients.
For the first time, with the IsoPlexis technology, we can identify and predict how these superhero cells orchestrate the immune response much earlier in the clinical process, using functional proteins (e.g., cytokines, chemokines, growth factors, etc.). In this manner, we can refine immunotherapies and targeted therapies at the cellular behavior level so that they are more precise and personalized.
AM: Can you let us know more about the Functional Cell Library and how it was built? What are the superhero and supervillain cells, and how are they identified?
The Functional Cell Library is a industry-leading collection of highly functional, proteomically driven cells, which have been uniquely identified by the IsoPlexis platform, that will determine how the human body responds to complex situations 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 range of high impact journals, the library identifies a broad spectrum of rare and substantial polyfunctional cells.
The Functional Cell Library, complementing the genomic information used in mapping the Human Cell Atlas, has added a unique layer of proteomic data on the wide spectrum of superpowered immune and tumor cell types identified by IsoPlexis'' unique functional proteomics. It provides the foundation to utilize unique functional phenotyping techniques to patient responses in vivo for preclinical, translational, and clinical applications.
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 findings across a wide variety of cell types for product manufacturing and quality control, as well as preclinical, translational and clinical applications.
Is there any information you can provide us on the publication of the Cell study? What were the most important findings?
SM: In this paper, researchers compared patient symptoms with the in-depth analysis of blood-based biomarkers throughout COVID-19 infection to identify factors associated with the development of post-acute sequelae of COVID-19 (PASC). A range of new, returning or ongoing health problems may be encountered four or more weeks following infection.
Authors followed 309 patients from initial diagnosis to early-stage recovery from acute disease, covering up to 23 months post-diagnosis to pinpoint the early causes that contributed to long COVID, such as the increased frequency of supervillain immune cells subsets.
Can you tell us about how the IsoPlexis single-cell functional proteomics platform helped to detect the presence of different immune cells and inflammation in a long-term COVID?
SM: Proteomotherapy for IsoPlexis single-cell patients provided a unique methodology to investigate the functional effects of different cell types across multiple times, as well as the relationship between innate and adaptive immune responses that contributed to effector function or inflammation in long COVID.
Proteicymetry from IsoPlexis revealed a correlation between the increased frequency of supervillain T cell subsets with type 1, type 2, and intermediate polarized PASC endotypes, indicating disease severity at convalescence. A single-cell functional analysis also demonstrates the supervillain monocytes in convalescent patients compared to healthy individuals who correlated with all four identifiable endotypes of PASC, indicating the impact of monocytes on long-term inflammation.
KB: The study has identified four endotypes of COVID-19 post-acute sequelae, and how might this information be used to guide treatment strategies?
Through understanding the supervillain cells that drive inflammation in COVID-19, we can apply these insights to a wider spectrum of critical challenges for inflammatory diseases, such as diagnosis and diagnosis. Our platform has previously been used to promote vaccination development as well as understanding the mechanisms of transplant rejection, cytokine release syndrome and toxicity, and autoimmune inflammation.
What other diseases and applications can benefit from single-cell functional proteomics, outside of COVID-19?
SM: Our unique-cell functional proteomics is critical for immune monitoring and immune health. In many studies, our readingout was uniquely predictive of patient attributes in research areas such as cancer immunology, cell therapy, autoimmune inflammation, and others.
Two recent Nature Medicine papers demonstrate the unique potential of IsoPlexis'' unique-cell proteomic platform for predicting the effectiveness of novel cell therapies, including chimeric antigen receptors (CAR) T-cells in blood cancer and tumor-infiltrating lymphocytes. One of the greatest challenges in improving cell therapies is understanding exactly how CAR-Ts and TILs function, which then leads to improved evaluations of quality, potency, and durability.
A blood-based biomarker was identified for patient response and progression-free survival in a Phase 2 clinical trial for combination checkpoint and new IL-2 agonist therapy, according to the Journal of Clinical Oncology.
What else would you like to mention in this article?
Duomic, a revolutionary technology that allows researchers to detect both functional proteomics and gene expression from a single cell, is ideal for researchers to develop functional proteomics and gene expression. This allows researchers to dive deeper into the genetic behind of those super cells, with applications in:
- 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