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

A New Approach Correlates Cell Therapy
Potency to In Vivo Outcomes
IsoPlexis' Polyfunctional Strength Index (PSIā„¢) can be
utilized to address these challenges, in particular to
provide metrics that uniquely relate the CAR-T cell product response to in vivo preclinical and clinical outcome
measures. Polyfunctional cells are recognized as key effector cells contributing to the development of potent and
durable cellular immunity against viral infection, cancer,
and other diseases.
To provide information about the sensitivity of the
cellular response, the IsoPlexis single-cell proteomics
platform uniquely captures the full range of relevant
cytokines from each immune cell connecting each cell
to the many cytokines they secrete that orchestrate the
immune system.
PSI is defined as the percentage of polyfunctional single
cells in a sample that secretes two or more proteins,
multiplied by the average signal intensity of the secreted
proteins from individual functional groups from each
cell. Each cell's strength, across one thousand or more
cells, is then aggregated and simplified to provide a
comprehensible visualization of the potent cell subsets
and the cytokine types that drive them.
The PSI metric has helped capture the potency of important and highly functional T-cell and other immune cell
subsets. Using PSI, researchers have identified cytokinebased biomarkers, which objectively evaluate the quality



of anti-tumor activity of CAR-T response, pre-therapy, in a
manner that correlates with in vivo outcome.
This new approach helps researchers better understand how T cells functionally respond to immunotherapies by evaluating the CAR-T cell product quality
in a scientifically rational manner. These types of
data will enable more precise medicine and improve
patient results in the future. PSI has also provided
mechanistic insights to improve the decision-making
process for choosing CAR-T cell and other immunotherapy lead candidates.
Discover: Revealing T-cell and Immunotherapy
Mechanism in Solid Tumors
Aldesleukin-recombinant Interleukin-2 (IL-2)-was the
first cancer immunotherapy approved by the FDA for
the treatment of metastatic renal cell carcinoma (1992)
and metastatic melanoma (1998). However, the administration of high-dose IL-2 results in pleiotropic effects
on the immune system including severe hypotension
and vascular leak syndrome, which has significantly
hampered its use.
IL-2 induces not only the desired expansion of tumorkilling CD8+ effector T cells, but also expands immunosuppressive CD4+ CD25+ regulatory T cells (Tregs), an
undesirable side effect. To maximize the efficacy of IL-2
therapy while mitigating side effects, PEGylated IL-2 was
generated and found to be profoundly more tolerable
than its non-PEGylated counterpart.

Identifying functional heterogeneity of phenotypically similar cells, on
the IsoCode Chip, helps reveal subsets of highly potent polyfunctional
anti-tumor T-cell subsets, that correlate to in-vivo patient response in
published immunotherapy studies.

IsoPlexis eBook

Table of Contents for the Digital Edition of IsoPlexis eBook

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IsoPlexis eBook - Contents
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