Single-Cell Functional Proteomics is Leading the Wave in CAR-T Therapies

The IsoPlexis Generation of Potency, Persistence, and Cellular Fitness

The world of CAR-T is rapidly accelerating, with the first two approved cell therapies from Kite Pharma and Novartis and 1000+ current cell and gene therapy trials. CAR-T therapies have quickly shifted the direction of treatments for aggressive diseases, such as blood cancers, where previous treatments were limited. However, determining cellular fitness is still a top need in moving the next generation of cell therapy treatments forward.

Cutting-edge cell therapies include both autologous and allogeneic options, and comprise T cells, NK cells, and more, while using technologies like CRISPR and TALEN to address blood cancers and solid tumors. CRISPR, for example, has opened up many possibilities in the cell therapy space, such as providing a way for researchers to develop a renewable source of NK cells to be optimized for cell therapies (Kaufman et al), as well as enabling more specific and targeted edits to cells in general.

A Better Definition of Fitness of CAR-T Cell Products with Recently Approved Therapies

During the first wave of approved cell therapies, Novartis published data using IsoPlexis’ single-cell functional platform to demonstrate enhanced ability to detect underlying cell therapy product heterogeneity. IsoPlexis’ single-cell cytokine based PCA visualizations (Figure 1) of the CTL019 CAR-T product, which published in JITC, revealed the potential to visualize donor and process differences.

PAT PCA Figure 1

Additionally, researchers at Kite Pharma used the IsoPlexis single-cell cytokine platform to correlate pre-infusion cell product data, a metric termed polyfunctional strength, with objective response in vivo for the first time. Importantly, existing technologies like flow and ELISA did not correlate with response (Figure 2), as published in Blood. In contrast to flow-based systems, where cells must be fixed and permeabilized, halting biological function and trapping cytokines within the cells, IsoPlexis’ single-cell cytokine system measures true releases of the full range of functional cytokines, which recruit other immune cells, destroying the tumor.

PSI Figure 2

IsoPlexis’ correlative CAR-T cellular fitness metrics are defined by their ability to capture truly released cytokine function of each cell. This knowledge is being applied in advanced bioprocessing with cell product biomarkers (Figure 3) and in donor selection in allogeneic cell therapies by leaders in the cell therapy field. See Figure 4 for quotes from Fred Hutch, City of Hope, Kite Pharma, and Moffitt Cancer Center.

CAR T Cells
Figure 3

Visit Our Biology page to learn more about our technology and see how IsoPlexis’ technology is determining the potency, persistence, and overall fitness of a cell therapy product, which is critical to accelerating engineered cell therapy development.

 

World Map and IsoLights
Figure 4

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