Why Difficult Combination Checkpoint Pre-Clinical Development Choice is Evolving with IsoPlexis’ Single-Cell Cytokine Analysis

Current Challenges in Checkpoint Therapy Development

2018 saw a rise in the number of active clinical immunotherapy trials utilizing checkpoint therapy. The complex phase of development in preclinical checkpoint and combination therapies experiences challenges relating to immune function and patient response. To address this need for optimization, IsoPlexis is providing better characterization of each T cell’s functional fitness and potency to advance the early stages of preclinical development. Additionally, IsoPlexis’ partnership with the NCI will help expand the pre-infusion quality characterization and correlative studies to address the need for cellular fitness and persistence in immunotherapies.

Novel Functional Profiling Correlating in vivo

IsoPlexis’ systems have achieved correlative data through novel functional profiling of tumor infiltrating lymphocytes (TILs) and T cells from checkpoint immunotherapy patients with single cytokine analysis (Figure). In a study with Yale, legacy technologies such as histology and multiplexed bulk serum cytokine analysis were unable to detect differences between patient responders and non-responders. IsoPlexis’ Polyfunctional Strength Index (PSI) significantly outperformed other bulk-level metrics in the ability to distinguish responders from non-responders.

In an additional study, Tesaro (a GSK company) characterized  the functional response of TILs treated with a triple combination therapy compared to single or double combinations. Increase polyfunctionality was associated with the triple combination therapy indicating more effective TILs activation.

Researchers Advance Checkpoint Trials Using Single-Cell Cytokine Detection System

Researchers at UCLA used IsoPlexis’ platform to characterize the immune function from novel combination agonist and cell therapies. The novel combination therapy was found to increase the polyfunctionality of antigen-specific T cells, which secrete cytokines associated with anti-tumor immunity. This combination activated a unique polyfunctional subset of cells, which correlated to response. “The IsoPlexis assay… is the most conclusive data we have obtained in this model system,” Dr. Antoni Ribas, Director of the tumor immunology program at the University of California Los Angeles’ Jonsson Comprehensive Cancer Center said.

Researchers at MD Anderson used the IsoPlexis system in an early clinical AML trial to analyze immune fitness and identify potential predictive biomarkers for patient outcome. In these combination nivolumab/azacitidine studies, the researchers showed that PSI is a potential predictor of response and overall survival in relapsed patients treated with this combination therapy.

IsoPlexis is advancing the characterization  of single-cell immune function, cellular fitness, and potency to accelerate the development of checkpoint therapies. Want to learn more? Check out our Tech Note, “Maximizing IsoPlexis System Single-Cell Data by Referencing Precedent Sample Preparation Protocols.”

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