Multiplexing Phenotype and Function for More Biologically Relevant Insights - 10

More Biologically Relevant Insights | SCREENING CHECKPOINT INHIBITORS

Results
Combinations of donor PBMC pairs were treated
with varying concentrations of anti-CTLA-4 and then
cytokine secretion, viability, and proliferation were
measured. Cytokine secretion variations were seen
between different donor pairs treated with antiCTLA-4, especially IFNγ. The anti-CTLA-4 antibodies
had no effect on cell viability or cell proliferation
(Figure 1, previous page).
In a second experiment, anti-CTLA-4, anti-CD73,
anti-PD-1, and anti-PD-L1 were combined together
in various permutations and added to a single donor
pair. Figure 2 shows IL-1β was increased when cells
were treated with anti-CD73 and anti-CTLA-4 and
when treated with anti-PD-1 and anti-CTLA-4. INFγ
was increased when cells were treated with a combination of anti-PD1 and anti-CTLA-4, a combination
of anti-CD73 and anti-CTLA-4, and a combination
of anti-CTLA-4 and anti-PD-L1. TNFα was increased
when cells were treated with a combination of antiPD1 and anti-CTLA-4, a combination of anti-CTLA-4
and anti-CD73, and a combination of anti-CTLA-4
and anti-PD-L1. Synergies ranging from 2-10 fold
increase over anti-CTLA-4 alone were observed in
the secretion of TNFα and IL-1β. Large scale multiplexed experiments allowed extensive profiling of
donor pair responses to treatment with checkpoint
inhibitors in a MLR (Figure 3). The Intellicyt® iQue
Screener PLUS enables this kind of experiment to
be run in 30 minutes. The ability to evaluate the
secretion of multiple assay endpoints provided the
construction of a comprehensive profile of checkpoint modulation with antibody combinations. n

Figure 2. Evaluating Combinations of Checkpoint Inhibitor Antibodies in Mixed Lymphocyte Reactions. Cytokine secretion
from a single donor pair was measured in response to four antibodies, alone and in combination, that target different immune
checkpoints. Synergistic responses were observed for some combinations and there were no changes in cell viability or
proliferation seen.

Figure 3. Differential Responses of Donor Pairs to Anti-CTLA-4 Antibodies in Mixed Lymphocyte Reactions. Cytokine responses
of eight pairs of donor PBMCs at a single concentration of anti-CTLA-4 antibody (17 μg/mL) were evaluated.

10

| January, 2019


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Multiplexing Phenotype and Function for More Biologically Relevant Insights

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Multiplexing Phenotype and Function for More Biologically Relevant Insights - Contents
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