Agilent - Breakthroughs in Immunotherapy- 2019 - 13

Breakthroughs in Immunotherapy

expressed in separate T cells (CARpool), as distinct
proteins within the same T cell (biCAR), or as a single
fusion protein within T cells (TanCAR). When incubated
with glioblastoma target cells each of these CAR T
approaches displayed differential killing capacity and
kinetics. These nuances in serial killing behavior are
readily elucidated by continuous impedance monitoring
but would go undetected in traditional end-point assays.
Another sensitive, time-resolved platform that can
deliver rich, functional data is the Agilent Seahorse
XF Analyzer (Agilent Technologies). A pivotal study
published by the Carl June group showed how different
CAR T engineering constructs can have dramatically differential effects on cell fate and function by
driving different metabolic programs8. It reveals how
one might optimize tumor elimination, persistence
in the microenvironment, and durability. In Figure 4,
a summary of their findings reveals how CAR T cells
containing the coreceptor signaling domain, 4-1BB,

Figure 4. Choice of T cell signaling domains impacts metabolic
programming differentially, introducing the possibility of finetuning cell-based therapies. 4-1BB containing CAR T cells are more
aerobic with increased mitochondria resulting in enhanced in vitro
persistence and central memory cell fate. In contrast, CD28 enforces
a more glycolytic program leading to increased effector memory.
Figure adapted from Kawalekar et al., Immunity 44, 380-390 (2016).
For Research Use Only. Not for use in diagnostic procedures.

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Figure 4

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Agilent - Breakthroughs in Immunotherapy- 2019

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