IsoPlexis eBook - 11

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

for CAR-T cells to predict response. No other immune profiling metrics provided the same type of deep useful data.
This study also uncovered unexpected findings. CD4+
T-cells with definitive cytokine signatures were more associated with response relative to CD8+ T-cells. Additionally, it
was found that levels of IL-15 and product PSI acted synergistically for an even more compelling metric to predict
At the 2018 American Association for Cancer Research
annual meeting, Parisi et al. presented a preclinical study
on a pmel-1 mouse model examining the effects of IL-2
and NKTR-214, a PEGylated IL-2, on the polyfunctionalities of T cells. PSI demonstrated that combination therapy
with adoptive cell transfer and NKTR-214 provided a robust
antitumor response in the aggressive B16F10 melanoma
The metric was also used to detect subtle differences in
CAR-T bioprocessing methods. These 2018 data by Srivastava et al. demonstrated that a modified manufacturing
method significantly improved the overall quality of CAR-T
cell products and allowed a deeper understanding of the
drivers of this polyfunctional upregulation for better cell
product characterization.5



The Future
In discovery and optimization, potent polyfunctional cell
subsets have revealed key differences between therapeutic
options in combination cell therapy, and cell therapy bioprocessing methods. In the future, PSI will certainly be applied
to a host of other large clinical problems and be built upon
to increase its utility even further. n
1. C. Ma et al. A clinical microchip for evaluation of single immune cells
reveals high functional heterogeneity in phenotypically similar T cells, Nat
Med. 2011 Jun;17(6):738-43. doi: 10.1038/nm.2375 
2. C. Ma et al., Multifunctional T-cell analyses to study response
and progression in adoptive cell transfer immunotherapy, Cancer
Discov. 2013 Apr;3(4):418-29. doi: 10.1158/2159-8290.CD-12-0383.
Epub 2013 Mar 21
3. J. Rossi et al., Preinfusion polyfunctional anti-CD19 chimeric antigen receptor T cells are associated with clinical outcomes in NHL, Blood. 2018 Aug 23;
132(8): 804-814. doi: 10.1182/blood-2018-01-828343: 10.1182/blood-201801-828343
4. G. Parisi et al., Enhanced expansion and tumor targeting of adoptively
transferred T cells with NKTR-214, 2018 American Association for Cancer
Research annual meeting
5. S. Srivastava et al., Abbreviated T-cell activation on the automated Clinimacs Prodigy device enhances bispecific CD19/22 Chimeric Antigen Receptor T-cell viability and fold expansion, reducing total culture duration, 2018
American Society of Hematology annual meeting

IsoPlexis eBook

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