IsoPlexis eBook - 14

Polyfunctional Strength Offers a New Approach to Defining Quality in Cell Therapy

What you are trying to do is engineer a patient's immune
system to attack their cancer, and there are inevitably going
to be consequences because of that. A tremendous amount
of research is focused on trying to understand how to avoid
autoimmune or neurological adverse events. Those types of
results are just now being physically resolved or will be over
the next few years.

processes and so separately optimizing them for
therapeutic performance is a reasonable near-term goal.
Poly-functional single-cell analyses can provide powerful
tools for such optimizations.

Dr. Heath: These single-cell functional analyses have been
pretty good across the board at differentiating responders
from non-responders, both during the course of therapy
and, in some published cases, in terms of analyzing CAR-Tcell products before they are even infused into the patient.
There are not many other metrics that have yet emerged
that give you that type of feedback.

One thing that is a bit of a challenge is that as CAR-T cells
have become more and more effective you still will have
adverse events. You have patients who do not respond
well. But you do not always see the sort of detailed molecular workup of the patients that you would need to understand if there is something about a patient that is limiting
the positive functional characteristics of the T-cells. To take
a related example, almost no patients with melanoma
tumors get biopsies anymore, because of the success of
checkpoint inhibitors. There are still patients who don't
respond, or who might respond badly to such immunotherapies, but there really aren't opportunities to study
such patients.

The analysis of CAR-T cells prior to infusion can guide and
help you anticipate patient response. This can provide
feedback on manufacturing because you want to control
the manufacturing process to optimize the tumor killing
properties of the T-cells, while also minimizing factors such
as T cell exhaustion. Those are two separate biological

It is my hope that as we continue to push new CAR-T cells
forward, these participating patients will be deeply studied
over the treatment course, and even beyond. That type
of patient participation is key to helping us aggressively
advance the science in a way that allows it to benefit
more patients. n

GEN: How might single-cell functional analyses
accelerate development of CAR-T therapies?



IsoPlexis eBook

Table of Contents for the Digital Edition of IsoPlexis eBook

IsoPlexis eBook - 1
IsoPlexis eBook - 2
IsoPlexis eBook - Contents
IsoPlexis eBook - 4
IsoPlexis eBook - 5
IsoPlexis eBook - 6
IsoPlexis eBook - 7
IsoPlexis eBook - 8
IsoPlexis eBook - 9
IsoPlexis eBook - 10
IsoPlexis eBook - 11
IsoPlexis eBook - 12
IsoPlexis eBook - 13
IsoPlexis eBook - 14
IsoPlexis eBook - 15