IsoPlexis eBook - 7

Polyfunctional Strength Offers a New Approach to Defining Quality in Cell Therapy

Predict: Correlating Pre-Infusion Product to Clinical Outcomes
Predicting patient response to cell therapy is a hurdle. Biomarkers that allow
clinicians to stratify patients into responders and non-responders and identify
those with an increased risk of adverse side effects, such as immunotoxicity, are
needed. PSI is positioned to be a powerful predictive tool to determine objective response to cell therapy.
In a 2018 publication in Blood by Rossi et al., pre-infusion CD4+ and CD8+ CAR-T
cell samples from 20 of 22 patients in a CAR-T clinical trial were profiled. The
study comprised a cohort of patients with aggressive refractory non-Hodgkin
lymphoma. The PSI of the pre-infusion CAR-T cell products, which combined
CD4+ and CD8+ CAR-T response, showed significant correlation with the objective response of patients. Specifically, the average PSI of the responder subgroup
was more than twice as high as that of the non-responders, a difference that
was statistically significant. PSI combined with CAR T-cell expansion or pretreatment serum IL-15 levels conferred additional significance.
PSI outperformed other pre-infusion metrics, including IFN-γ co-culture cytokine intensity, ratio of CD4+ to CD8+ T cells, and various T-cell phenotype
frequencies, and was the only metric that statistically differentiated responding from non-responding patients. These results indicate the metric's potential
as a biomarker for guiding personalized CAR-T cell treatments and potentially
predicting therapeutic efficacy.
While overall PSI correlated with clinical outcome, a study was undertaken to
better understand which cellular and cytokine subsets of the CAR-T product PSI
associated mostly strongly with outcome. Since CD8+ T cells are known to have
effector and tumor-killing properties, it was hypothesized that the CD8+ subset
would drive the increase in PSI.

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| GENengnews.com

IsoPlexis' Systems provide physiologically relevant readouts empower decisions across
the workflow from Lead Discovery, Optimizing Bioprocessing, and Biomarker correlates.
These correlates then feed back into the funnel, driving more informed decisions
through the drug development pipeline.


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IsoPlexis eBook

Table of Contents for the Digital Edition of IsoPlexis eBook

Contents
IsoPlexis eBook - 1
IsoPlexis eBook - 2
IsoPlexis eBook - Contents
IsoPlexis eBook - 4
IsoPlexis eBook - 5
IsoPlexis eBook - 6
IsoPlexis eBook - 7
IsoPlexis eBook - 8
IsoPlexis eBook - 9
IsoPlexis eBook - 10
IsoPlexis eBook - 11
IsoPlexis eBook - 12
IsoPlexis eBook - 13
IsoPlexis eBook - 14
IsoPlexis eBook - 15
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