GEN-IsoPlexis_RT_Nov22_Single-CellAdvances - 4

ROUND T ABLE
GEN: What are some of the recent advancements
and current strategies for developing
immune-based therapies as well as strategies for
overcoming difficult to treat diseases and why
is single-cell function an important part of the
equation?
Peggy Sotiropoulou:
Immunotherapy, specifically T cell therapy and immune
checkpoint blockade, has demonstrated remarkable success
in cancer treatment in recent years. We know the immense
success of CAR-T cells in hematologic malignancies, but
adoptive cell therapy for solid tumors is lagging.
A recent milestone in the advancement of TCR-based
therapy for solid tumors was the regulatory approval
earlier this year of a gp100 TCR bispecific developed by
Immunocore. Other announcements this year included a
BLA submission for the first TCR-T therapy developed by
Adaptimmune Therapeutics and a BLA submission for the
first TIL therapy from Iovance Biotherapeutics. We had an
especially important and productive year for cell therapy for
the treatment of solid tumors.
T cell products (both autologous and allogeneic) are
heterogeneous in nature, and this is a roadblock toward
identifying predictive biomarkers that are correlated with
strong efficacy and a favourable safety profile. However, by
using single-cell proteomics, a precise assessment of each cell
type in the heterogeneous T cell product can be correlated
with clinical outcome, including both efficacy and safety, for
the development of better therapies.
Abhishek Garg:
In a broad sense, there are three parallel advancements
that are currently defining trends and strategies for anticancer
immunotherapy. There is enthusiasm and a big push
toward alternative immune checkpoints targeting antibodies
e.g., immunotherapies targeting LAG3, TIM3, TIGIT, or
VISTA. The recent success with LAG3-targeting antibody in
melanoma is, perhaps, the first example of early success in
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this arena. Other examples, like TIM3 or TIGIT, are going
in a direction that people may not like but the final clinical
verdict is still pending.
Then, going beyond this, the so-called generation 4
of CAR-T cells, i.e., T cells integrating tumor microenvironment-modulating
agnostic or antagonistic ligands or
cytokines, apart from CAR constructs, are gaining strong
momentum. Lastly, there is a T cell therapy-based push
towards solid tumors in the form of TCR-specific cell
therapies. Herein, understanding the single-cell function will
be necessary because most of the specific tumor susceptibility
or resistance pathways applicable to the aforementioned
immunotherapies would not be identical to those already
known from anti-PD-1/anti-CTLA4 antibodies, thereby
requiring a high-resolution single-cell view of mechanisms
or pathways mobilized by these immunotherapies.
Luca Gattinoni:
I agree with Abhishek that immune checkpoint inhibitors
and T cell transfer are the main advancements in immunotherapy.
There is also a push toward the development of
therapies targeting neoantigens that are beginning to show
great success as evidenced by the remarkable response of
a pancreatic cancer patient who received neoantigen T cell
receptor-engineered T cells that was recently reported in the
New England Journal of Medicine.
GEN: How can single-cell technologies such as
single-cell functional proteomics reveal insights
into the development of better therapies?
Luca Gattinoni:
Single-cell technologies, including single-cell functional
secretomics, provide a deeper characterization of T cell
products and inform us on their therapeutic potential. We
employ these assays to rapidly evaluate the impact of new
pharmacologic or gene-engineering approaches aimed at
improving T cell function and to determine which strategies
to pursue for further development. Indeed, single-cell
functional proteomics can reveal differences in cytokine
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GEN-IsoPlexis_RT_Nov22_Single-CellAdvances

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