Isoplexis_July2021_AcceleratingDevelopmentCurativeMedicines - 13

goal of solid tumor research. Oncolytic immunotherapy
with engineered adenoviruses (OAd) and
helper adenovirus can disrupt the TME and stimulate
CAR-T cells, enhancing the host anti-tumor immune
response. Together, these viruses are referred to as
combinatorial Ad vector (CAd). McKenna, et al. developed
CAR-T cells to target HER.2
of group of cancer cells that were co-cultured with
uninfected MSCs and without CAR-T cells, treatment
with CAd MSCs combined with CAR-T enhanced
CAR-T function, leading to a reduction in tumor
, a receptor expressed
in tumor types including breast, lung, and sarcoma.
Then, researchers added CAd to help further stimulate
the immune response to the CAR-T treatment.3
Unfortunately, intralesional administration of
CAd is challenging for many tumor locations, and
intravenous administration is impossible in some
patients who have innate or adaptive responses to
the therapy due to prior exposure to adenovirus.
To shield the viruses from immune recognition,
researchers used mesenchymal stromal cells (MSCs),
which provide an environment for viral replication
and release the viruses directly to tumor sites to
avoid neutralization by the immune system.
To test the effects of treatment with CAd MSCs
and clinically validated tumor-directed HER.2 CAR-T
cells, McKenna, et al. co-cultured CAd-infected
MSCs with two non-small cell lung cancer cell lines
(A549 and H1650).3
After 48 hours of co-culture, the
researchers added either non-transduced (NTR) cells
or CAR-T cells. Residual tumor amount was then
quantified at 48, 72, and 96 hours post-treatment
with the NTR or CAR-T cells. Compared to a control
Additionally, compared to treatment with
HER.2 CAR-T alone, the combination of CAd MSCs
with HER.2 CAR-T cells significantly reduced tumor
cell viability.3
Single-Cell Secreted Proteomics Identifies
Upregulated T Cell Polyfunctionality
Associated with Improved AntiTumor
Function of CAR-T Cells
Treated with CAd-Infected MSCs
McKenna, et al. used IsoPlexis' functional single-cell
proteomics to investigate the mechanisms through
which CAd-infected MSCs improve HER.2 CAR-T cell
efficacy. The Single-Cell Secretome solution was
used to measure the polyfunctionality of individual
T cells. In previous studies, polyfunctionality has
been associated with anti-tumor activity and has
predicted clinical outcomes.4,5,6
IsoPlexis' single-cell
secreted proteomics found that CAd MSC-treated
HER.2 CAR-T cells that were co-cultured with tumor
cell lines were more polyfunctional than those that
were not treated with CAd MSCs (34% and 40% of
CD4 and CD8 cells, respectively). In comparison,
the untreated HER.2 CAR-T cells had CD4 and
CD8 polyfunctionality rates of only 5% and 16%.
Infection with CAd MSCs was also associated with | 13


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