Agilent - Breakthroughs in Immunotherapy- 2019 - 29

Breakthroughs in Immunotherapy

GEN: Why is it important to measure target cell killing directly
rather than by quantifying related factors such as levels of
secreted compounds or the activation of effector cells?
Dr. Anderson: Both are important, but it's especially important to
measure target cell death because every tumor is a little different.
Some tumor cells may respond to one killing mechanism and not
to another, and because they are also so readily able to adapt to
evade T cell-mediated killing, we need to be able to see that the
T cells can actually kill the targets.
It is important to note that the xCELLigence assay isn't technically
a direct readout of cell killing, it's a measure of impedance, which
reflects the ability of the target cells to adhere to the bottom of the
plate. Since dead cells do not impede the signal, this is an indirect
readout of cell killing. For the purposes of our experiments, it has
yielded the most reproducible results and allowed us to study
physiological effector-to-target ratios that we couldn't evaluate
using the other assays.
Dr. Overstreet: If what you ultimately want to see is how a T cell
interacts with a tumor cell and kills it, then that's what you should
be measuring. T cells have an array of overlapping/semiredundant
ways of killing a target cell, and by choosing to measure a single
analyte, you could be missing the critical limiting factor in the
particular interaction. But if you look at how a tumor cell is dying
in real time, then you can see that dynamic interaction that is the
net result of all the effector functions, and you can observe how
your therapeutic can alter that interaction.
29

| GENengnews.com

Michael Overstreet, Ph.D.
Scientist, MedImmune
(a unit of AstraZeneca)

"One advantage of xCELLigence
assays compared to traditional
means of evaluating T-cell toxicity is
the greater specificity."

http://www.GENengnews.com

Agilent - Breakthroughs in Immunotherapy- 2019

Table of Contents for the Digital Edition of Agilent - Breakthroughs in Immunotherapy- 2019