Agilent - Breakthroughs in Immunotherapy- 2019 - 28

Breakthroughs in Immunotherapy

sorting (FACS) to look at CAR T-cell killing, but it gives a very indirect
measure, and it lets you look only at a snapshot in time. You can't
see how your CAR T cells or cancer cells are evolving over time.
You need a technology that allows you to look at the co-culture of
your cancer cells and CAR T cells over time to be able to identify the
correct distribution of naïve or central memory to effector memory
T cells. You need to be able to determine how long it takes these
cells to mature so you get to see when cell killing occurs, on the
opposite end of the spectrum, when CAR T cells become exhausted
and the cancer cell population starts to grow again. Being able to
see what happens in real time is critical to your CAR design and
how you culture your CAR T cells in vitro to get the proper subtype
distribution.
Dr. MacLeod: One of the main challenges is being able to translate
the in vitro results to how the therapy will actually perform in vivo,
either in animal models or in patients. The traditional assays for
measuring cytotoxicity are usually short, sometimes 3 or 4 hours,
and to see a response, you use very high effector-to-target cell
ratios. This will show activity, but it doesn't reflect the entire mechanism of action.
These are living products-they don't just kill cells, they also proliferate, and that's an important part of the mechanism. When you
are able to look at killing of target cells over longer periods of time
at lower effector-to-target ratios, that allows the effector cells to
proliferate and kill multiple targets-what is called serial killing-and
that type of longer assessment is a much more stringent way to
evaluate T-cell activity.
28

| GENengnews.com

Dan MacLeod, Ph.D.
Associate Director, Cell Therapy Discovery
Precision BioSciences

"These are living products-they don't
just kill cells, they also proliferate,
and that's an important part of the
mechanism."

http://www.GENengnews.com

Agilent - Breakthroughs in Immunotherapy- 2019

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