eBook: Cell and Gene Therapy - 8

Luciferase Reporter Cancer Cell
Lines Facilitate CAR-T Development
These novel in vitro tools have high endogenous expression of CD19,
CD20, or HER2, making them more physiologically relevant.
John Foulke, MS; Luping Chen, BS; Brian Della Fera, BS; Hyeyoun Chang, PhD;
Kevin Tyo, PhD; Zhizhan Gu, PhD; and Fang Tian, PhD
Abstract
Chimeric antigen receptor (CAR)-T cells have displayed
remarkable efficacy in treating malignant
cancers, particularly liquid tumors. CAR-T cells have
proven to be a new type of " living " therapeutic that
harnesses the patient's immune system to recognize
specific tumor-associated antigens and redirects
the engineered T cells to more specifically target
tumor cells.1
Considerable research efforts have
been invested into developing new CAR structures
to increase the scope of targeted cancer types and
raise their antitumor efficacy.2
Evaluating the biofunction
of CAR-T cells in vitro typically involves a
series of labor-intensive co-culture experiments
and immunoassays, where reproducibility remains
a challenge during the validation of new CAR-T
cells due to donor-to-donor variation and other
possible factors.3
In this study, we present CAR-T
Target Luciferase Reporter Cells that have high endogenous
expression of CD19, CD20, and HER2,
which makes them more physiologically relevant
as in vitro tools to develop adoptive CAR-T cell therapies.
These liquid and solid tumor cell lines exhibit
sensitive and stable luciferase reporter expression
that can be used to measure the potency and efficacy
of a wide range of CAR structures engineered
into T cells for autologous therapy.
Introduction
CAR-T cell-based therapeutics have emerged as
a promising immunotherapy for treating specific
leukemias, lymphomas, and myelomas. In this exciting
approach to treating refractory cancers, T
cells are isolated from a patient's blood via apheresis.
The cells are then incubated with the cytokine
interleukin 2 and anti-CD3 antibodies to stimulate
proliferation. Ex vivo silencing of genes involved
in graft rejection is conducted to aid in improving
T-cell stability after infusion. Once expanded, the
appropriate CAR is introduced into the cells by retroviral
transduction. These effector CAR-T cells are
then infused back into the patient where they can
exert their cytotoxic effects on tumor cells.1
8
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