Characterizing Engineered Cell Products with Single-Cell Functional Analysis: Case Studies Presented at the 7th Annual CAR-TCR Summit

IsoPlexis recently presented data at the 7th annual CAR-TCR Summit, a meeting dedicated to bringing together experts in cell engineering to foster learnings about the development and manufacturing of engineered cell therapies.

Chimeric antigen receptor (CAR) and T cell receptor (TCR) therapies have been shown to have striking therapeutic potential for the treatment of cancers and other malignancies, but there is still room for optimization. Identifying key quality metrics that are predictive of product potency or persistence can help to improve clinical outcomes, develop personalized therapy, and guide the development of new products. Manufacturing processes must also be optimized to robustly expand therapeutic material while still maintaining product quality. To achieve these endpoints, sophisticated techniques that can capture the full range of biological functions must be used.

Analyses that average cell characteristics or functions across many cell populations, can miss key individual functional differences. Assessing cells at the single-cell level provides higher resolution insights into product characteristics and functional heterogeneity, leading to more powerful, actionable data. IsoPlexis’ single-cell analysis solution is a platform that measures up to 32 cytokines secretions at the single-cell level using an automated workflow.

By analyzing functional secretions for each individual cell, IsoPlexis’ platform generates unique functional metrics, including polyfunctionality (the ability of a cell to secret two or more cytokines) and polyfunctional strength index (PSI; a unique IsoPlexis metric that combines polyfunctionality with cytokine secretion intensity to describe overall functional potency). These metrics have helped to evaluate engineered cell products at all stages of the developmental pipeline, and some of these findings were highlighted in a poster presented at the CAR-TCR Summit.

Using Single-Cell Functional Analysis to Evaluate Engineered Cell Therapies

IsoPlexis’ single-cell functional analysis platform has been used in a number of studies to characterize TCR-T and CAR-T products where polyfunctionality was assessed to confirm cell product functionality after gene edits, changes to receptors, and cell expansion. These studies, highlighted at the CAR-TCR Summit, demonstrate the utility of using polyfunctionality and PSI as an indicator of product quality and efficacy across a variety of applications.

In addition to product characterization, single-cell functional analysis can also help to identify both pre- and post-treatment biomarkers. When assessing cell products before infusion, IsoPlexis’ platform can be used to identify biomarkers that correlate with multiple important clinical metrics including response, relapse, progression-free survival, and the risk of adverse events. In one highlighted study, the PSI of pre-infusion CD19 CAR-T cells was the only metric identified that was significantly associated with response in non-Hodgkin lymphoma. The response to other types of engineered cell therapies can also be evaluated using single-cell functional proteomics for immune monitoring to assess key product characteristics, including response, persistence, and proliferation. For instance, tracking the polyfunctionality of peripheral CD4+ and CD8+ T cells after an infusion of tumor-infiltrating lymphocytes (TILs) revealed enhanced polyfunctionality for 12 weeks, demonstrating the persistence of the therapy against metastatic lung cancer.

Applying Polyfunctionality and PSI to All Stages of the Development Pipeline

From early development decisions to predicting clinical response, using single-cell functional proteomics to assess polyfunctionality and PSI can give researchers better insight into the function and quality of engineered cell products. By providing the single-cell data needed to fully evaluate product characteristics and efficacy, IsoPlexis’ Single-Cell Secretome solution is helping to optimize cutting-edge engineered cell therapies, such as CAR-T and TCR therapies, advancing clinical treatments and improving clinical outcomes.

Learn more about how leading researchers are using single-cell functional proteomics to combat the world’s toughest diseases in our newest roundtable eBook, Single-Cell Advances in Functional Immune Monitoring for Developing Immune Therapies and Uncovering Disease Pathogenesis. Download below!

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