Agilent - Breakthroughs in Immunotherapy- 2019 - 7

Breakthroughs in Immunotherapy * Interview with Dr. Carl June

Metabolic assays such as Seahorse, are
well poised to identify those cells, with
those properties. I see in the future that
there may be cell-based release assays
for potency, and also predictive assays, as
biomarkers of response in cell products.
David Ferrick: It's amazing what's
happened so quickly. To think there
would be, as you point out, this qualitative dichotomy between mitochondrial
respiration and glycolysis that fits immune
functionality so well-but hey, here we are.
One question we hear regarding this 'newer
type' of cell-based assay is about functional
potency testing in terms of what the new
product can do, and how long it will be able
to perform. What do you see?
Carl June: One potential use of these new
kinds of assays for cell analysis [Agilent
ACEA xCELLigence, Agilent Seahorse XF]
may be the ability to know which individuals could possibly make a curative
product with current technologies and in
others it would be futile. If you determine
that an individual is not a good candidate,
then that means you would go down the
line of using third-party cells for instance,
7

| GENengnews.com

so that's going to be a major change in
the future. In addition, even in candidates
where you determine you can manufacture
a successful product, another application
of this new "tool kit" may be finding, if you
will, the heavy lifters. Some assays have
shown, that when you do adoptive transfer,
the T cells that carry out most of the tumor
elimination are the progeny of just a few
cells. If we can identify those T cells, up
front, then potentially we can manufacture
fewer cells, meaning the cost of manufacturing would go down, leading to a number
of benefits in treatment.
David Ferrick: To follow up on that, how
do you see some of the newer technologies like CRISPR being used to increase
the fidelity and minimize the footprint of
cell engineering so that we can get that
protective immunity with a more natural
approach which may be the key to durability and minimal side effects?
Carl June: There are a few genome-wide
discovery approaches that identify 'targets
of opportunity' in T cells that, in preclinical
models, enhance their performance. It's a
great time because of these technological

advances in genome editing using CRISPR,
meganucleases, and so on, that make this
possible.
The issues are somewhat different
between solid tumors and hematologic
malignancies. In hematologic malignancies, T cells, after infusion, generally traffic
right to the bone marrow, that's a natural
aspect to them. But in solid tumors, it may
be rate limiting in many instances for T
cells to enter the solid tumor. So, strategies
that edit T cells to enhance their homing,
penetration, and persistence of the solid
tumor microenvironment are of great
interest.
Another opportunity is the tumor and T
cell "tug-of-war" between metabolites,
and where CRISPR engineering can help
increase access to nutrients in the tumor
microenvironment. CRISPR approaches
can help develop cells that are resistant
to that tug-of-war situation, so they can
survive longer, and therefore proliferate
better in a solid tumor microenvironment.
David Ferrick: That leads me to cell manufacturing and the QA/QC component of
http://www.GENengnews.com
Agilent - Breakthroughs in Immunotherapy- 2019

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