Isoplexis_July2021_AcceleratingDevelopmentCurativeMedicines - 15

which the CAd-infected MSCs enhance the efficacy of
CAR-T cells.
This anti-tumor activity correlated with the
results from a subsequent in vivo mouse lung cancer
model, demonstrating that IsoPlexis' technology
can provide insights with strong correlations to in
vivo biology CAd MSCs combined with HER.2 CAR-T
cells significantly reduced tumor growth compared
to either treatment alone.3
While CAd MSCs alone
did not reduce tumor expansion, the combination
of CAd MSCs with the NTR T cell group prevented
tumor growth from day 10 to day 22. Furthermore,
only the mice that received both CAd MSCs and
HER.2 CAR-T cells were able to prevent tumor
growth upon second challenge with the same A549
tumor line.3
Analysis of blood, spleen, and lung T
cells showed that CD8+ T cells in the CAd MSC plus
CAR-T cell group exhibited reduced expression of
the exhaustion marker Tim3 compared to the CAR-T
only group, indicating that the CAd MSCs promoted
T cell persistence. in vivo studies using an H1650
xenograft lung tumor model produced results that
were consistent with the A549 line: combination
treatment led to complete clearance of tumors
within 2 weeks, with no negative effects observed.3
The results of the study revealed mechanisms
behind anti-tumor activity with the unique
combination of CAd MSCs and CAR-T. Combination
treatment improved T cell infiltration and enhanced
effector cell function. Furthermore, combination
treatment enhanced T cell polyfunctionality, and
polyfunctionality was associated with improved
anti-tumor activity. The results of this study highlight
a potentially powerful combination therapy for solid
tumors and provide further validation for the use
of the polyfunctionality metric to predict clinical
outcomes and evaluate CAR-T product quality
and function. n
Watch our on-demand webinar with
Katie McKenna, lead author of this
study, to learn more.


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