Agilent - Breakthroughs in Immunotherapy- 2019 - 12

Breakthroughs in Immunotherapy

vation with adoptive cell therapies is that when cancer cells
expressing the targeted antigen are killed off, cells that lack
the antigen continue propagating undeterred. To minimize
this phenomenon, the authors targeted two tumor cell
antigens simultaneously and used xCELLigence to assess
both function and persistence. The results shown in Figure
3a enabled the authors to choose the optimal engineering
constructs based on a very sensitive quantification of the
killing efficacy using low effector to target ratios of various
combinations of costimulatory domains with a constant
antigen binding domain (N. Ahmed, unpublished results).
Simultaneously, they were also able to identify potential
escape phenotypes due to the time resolution of the assay.
In Figure 3b, key results are shown for different scenarios
where CARs targeting the HER2 and IL13Rα2 antigens were

Figure 3A

Figure 3B
Figure 3a. Various combinations of proprietary costimulatory domains
with a constant antigen binding domain were quantified for killing
efficacy using a low target to effect ratio (1:10) and simultaneously for
identification of potential escape phenotypes (pink and orange lines)
based on time resolution of the data (N. Ahmed, unpublished results, April
2, 2019).
Figure 3b. Using xCelligence to monitor the killing of the glioblastoma
cell line U373 by CAR-T cells targeting either one or both of the antigens
HER2 and IL13Rα2. In the figure legend: U373 = target cell line alone; NT
= target cells treated with nontransfected T cells (i.e. not expressing a
CAR); IL13Rα2 = target cells treated with T cells expressing a single CAR
targeting IL13Rα2; Her2 = target cells treated with T cells expressing a
single CAR targeting Her2; see text for descriptions of CARpool, biCAR,
and TanCAR. 1:10 E:T ratio. Figure adapted from Hegde et al., J Clin
Invest. 2016 Aug 1;126(8):3036-52.

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Agilent - Breakthroughs in Immunotherapy- 2019

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