IsoPlexis eBook - 6

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

PEGylated IL-2, NKTR-214, retains the same amino acid sequence as aldesleukin.
The IL-2 core is conjugated to six releasable polyethylene glycol (PEG) chains. In
the body, the PEG chains slowly release to generate active IL-2 conjugates to
provide sustained signaling to preferentially activate and expand effector CD8+ T
and NK cells over Tregs in the tumor.
At the AACR annual meeting in 2018, researchers from University of California
Los Angeles, IsoPlexis, and Nektar Therapeutics presented a preclinical study on
a pmel-1 mouse model, "Enhanced expansion and tumor targeting of adoptively
transferred T cells with NKTR-214." The research team examined the effects of
IL-2 and NKTR-214 on the polyfunctionalities of T cells in both tumor infiltrating
lymphocytes and the spleen. The study demonstrated that combination therapy
with adoptive cell transfer (ACT) and NKTR-214 provided a robust antitumor
response in the aggressive B16F10 melanoma model.

IsoPlexis' systems uncover the polyfunctional subsets of cells which are contributors
to response amongst the heterogeneity of patients. IsoPlexis' unique ability to uncover
differences in patient's T-cell fitness, uncovers the correlates to patient response as
published in Blood (2018).



The PSI of the murine CD8+ T cells after ACT-NKTR-214 combination therapy
was found to be significantly higher than the PSI of CD8+ T cells after ACT-IL-2
control treatment in both the spleen and tumor infiltrate. This type of insightful
knowledge of T-cell potency of the treatment, driven by the PSI, which correlates to in vivo performance in mice, can be of crucial assistance in revealing lead
choice in a variety of combination immunotherapy contexts.
Results suggest that PSI can help to reveal new mechanisms that enhance
lead choice not only in immunotherapies against solid tumors but also when
combining multiple complex immunotherapies to achieve eradication of
tumors. With better understanding of the underlying mechanisms of combined
immunotherapies, the design of immunotherapy strategies will improve, and
further advances will be made to help treat and eradicate cancer.

IsoPlexis eBook

Table of Contents for the Digital Edition of IsoPlexis eBook

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
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IsoPlexis eBook - 14
IsoPlexis eBook - 15