Bridging Genomics and Proteomics to Drive Highly Potent Allogeneic Therapies

The market for allogeneic cell therapies is rapidly growing. Driven by the ability to produce “off-the-shelf” products for a wide range of conditions, patients can receive treatment faster, which is particularly important in cases where there is rapid disease progression.

Researchers use gene-editing techniques to develop these therapies, however studies have shown that the correlation between genomic and transcriptomic sequencing and direct cytokine secretion is low, underscoring the importance of functional characterization of engineered cells.1

The ability to directly measure the function of individual immune cells is critical for revealing insights into potency, durability and other product quality metrics. Because immune cells can have varying levels of function, off-the-shelf therapy products can also vary in potency and product quality. IsoPlexis’ platform reveals the highly proteomically multi-functional “superhero” immune cells that orchestrate immune response. The presence of these cells is a key predictor of early and persistent response to cancer, efficacy of vaccines, and overall survival, as published in various high impact journals. IsoPlexis’ platform can provide critical cell quality attributes that guide product QC and manufacturing decisions in the cell therapy development pipeline.1

Allogeneic Therapies Bring Potency Challenges

While the prospect of allogeneic therapies is promising, there are still many challenges. Apart from toxicity and rejection, engineered and gene-edited cells can have functional differences after initial modification. Directly measuring single-cell functionality can reveal key insights into product quality. With the IsoPlexis platform, researchers can detect the highly functional superhero cells, which are undetectable with traditional technology. IsoPlexis’ platform analyzes the true function of each cell, thereby providing critical insight into cell therapy attributes.1

IsoPlexis’ Duomic™ Bridges Gap Between Genomics and Functional Proteomics

Immune cells, the drivers of response, are highly heterogeneous, which further complicates cell analysis and the development and optimization of effective immune therapies. Traditional technologies like genomics, bulk ELISA, and flow cytometry can estimate cellular function at the population level, but these differences do not reflect differences in function. The proteome is complex and requires direct detection. Dynamic in vivo biology is the captured by the proteome– the key to advancing medicines.

IsoPlexis has become the standard in identifying the single superhero cells that produce proteomic reactions that form many of the earliest signals of long-term response against diseases like cancer, infectious disease, and inflammatory diseases. These rare subsets of cells have correlated with biological response in vivo in multiple datasets. IsoPlexis is now leveraging the ability to perform both sequencing and functional proteomics, diving into the genetic and functional drivers of these individual supercells, for the first time.

IsoPlexis’ new proteomic and transcriptomic platform, Duomic, allows researchers to simultaneously measure functional protein and gene expression levels from the same cell. The  Duomic platform is an application for the next frontier of functional single-cell analysis and involves integrating direct in vivo proteomic activity from cells with the gene regulatory networks driving those reactions. Duomic utilizes the seamless, hands-off workflow and automated analysis of IsoPlexis’ instrumentation, delivering actionable multi-omics data to accelerate pathway discoveries while bridging transcriptomic analysis to real-time, in vivo proteomic activity.

IsoPlexis presented at SITC to demonstrate how to leverage powerful, proteomically active single cells and their genetic drivers, identified simultaneously via single-cell transcriptomic and proteomic analyses on IsoPlexis’ new Duomic platform. Engineered to correlate a cell’s instruction with its function, Duomic captures both mRNA expression data and highly multiplexed functional protein activity. The system brings transcriptomics and functional proteomics together to create an integrated multiomic platform. Integrative data analysis was performed using IsoSpeak software, and data was obtained with Duomic technology that analyzed the genetic drivers of the biologically powerful responses. These data provide insight into the link between polyfunctionality and the genetic make-up of individual cells.1

The ability to measure the direct function of single-cells is critical to predicting disease progression, cell therapy quality, and more. IsoPlexis’ functional proteomics is providing critical product quality metrics in the development  of both autologous and allogeneic therapies, through the discovery of powerful superhero cells, and now, for the first time, researchers can obtain single-cell transcriptomic and proteomic information simultaneously from the same single-cell, uncovering the genetic drivers of those superhero cells, critical to potency, persistence, and durability. IsoPlexis’ Duomic technology connects polyfunctional superhuman cells to their genetic drivers, helping to advance curative medicine across a range of complex diseases.

References

  1. https://isoplexis.com/blog/next-generation-quality-and-potency-metric-for-allogeneic-car-t-cell-products/
  2. https://www.genedata.com/news/details/autologous-allogeneic-cell-therapies
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