Overcoming Challenges in Cell Therapy Development: Optimizing Cell Therapy QC & Manufacturing (Part 2)

In Part 2 of “Overcoming Challenges in Cell Therapy Development” we’ll discuss the importance of using IsoPlexis’ single-cell functional proteomics to optimize manufacturing and ensure product QC of cell therapy products.

Importance of Single-Cell Functional Proteomics to Assess Cell Therapy Product Quality

A major challenge in the development of cell therapies is the identification of quality indicators of potency and persistence in the manufacturing and bioprocessing stage. Characterizing product fitness before the clinic is critical yet has proven challenging as status quo technologies offer only indirect measurements of cellular function. Optimization of cell therapy bioprocessing for enhanced therapeutic activity requires analysis of function through cytokine analysis at the single-cell level.

IsoPlexis’ IsoCode Single-Cell Secretome solution can directly identify a range of cytokines secreted by individual cells, giving researchers unique insights into cellular function. This enables the discovery of highly polyfunctional cells that can carry out numerous functions by secreting multiple cytokines simultaneously, which have been associated with improved activity and response. Optimizing manufacturing processes that yield highly polyfunctional cells can lead to cell therapy products with enhanced quality and fitness for improved clinical outcomes.

The following case demonstrates how IsoPlexis’ Single-Cell CAR-T Protocol has empowered researchers in the development of potent and persistent cell therapies.

Optimizing Manufacturing Processes for Potent CAR-T Products

In a recent study published in Nature Medicine, researchers Spiegel et al. used IsoPlexis’ platform to uncover new ways to optimize the manufacturing of a novel, bispecific CAR-T product targeting CD19 and CD22 (CD19-22.BB.z). In a Phase 1 clinical trial assessing treatment of recurrent or refractory B cell malignancies, IsoPlexis’ single-cell functional proteomics provided meaningful product quality insights to predict CAR-T potency in vivo.

The data from the trial suggest that progressive disease after CD19-22.BB.z-CAR in large B cell lymphoma (LBCL) is associated with a robust early response followed by early acquired resistance. Researchers identified a functional driver of relapse, suggesting possible improvements in CAR manufacturing that could prevent antigen escape-associated resistance.

The researchers found that functional protein production from single cells is a meaningful attribute to predict the potency of CAR-T cell therapies. The authors stated:

Our results suggest that engineering iterations should be guided by careful studies of single-cell CAR polyfunctionality incorporating cytokine production as a critical quality attribute.”

This publication highlights how IsoPlexis is providing critical predictive metrics for the product characterization and optimization of CAR-T therapies and manufacturing workflows.

Incorporating Polyfunctionality as a Cell Therapy Quality Attribute

IsoPlexis’ single-cell functional proteomics solution empowers researchers to phenotype individual immune cells by measuring extracellular function, providing predictive quality insights into cell therapy performance. Check out other published studies that demonstrate the unique utility of IsoPlexis’ single-cell proteomic platform for the development of cell therapies.

In part 3 of this series, we’ll highlight how leading cell therapy researchers are using IsoPlexis’ platforms to uncover unique biomarkers for predicting patient response. 

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