eBook: Cell and Gene Therapy - 5

and are difficult to scale up to industrial levels.6,7
Improving the reproducibility and productivity of
these cells, as well as minimizing contamination,
are essential steps for manufacturing and delivering
safe, effective therapies to the patients that
need them the most.
Advancing cell therapies with
optimized cell lines
One of the most promising cell therapies is chimeric
antigen receptor (CAR)-T cell therapy.8
This
immunotherapy is used to treat several cancers;
however, its utility is largely limited to liquid tumors
(B cell leukemia and lymphoma).8
A considerable
amount of work is being done to develop
CAR-T cells with improved efficacy for a wider
range of cancer types.9
Testing the functionality
and efficacy of these cells requires time-consuming
and labor-intensive co-culture experiments
and immunoassays. These assays often suffer from
variable and irreproducible results, largely due
to donor-to-donor variation in the primary cells
used.8
Additionally, the traditional 51
Cr release assay
for quantifying cytotoxicity is radioactive, requiring
specific protective measures both while
running the assay and while disposing of materials.
Alternative assays suffer from considerable
intra- and inter-assay variability, making them unsuitable
options.
Driving gene therapy and vaccine
development with cell lines capable
of producing high-titer viral stocks
Gene therapies are often discussed in tandem
with cell therapies. These therapies manipulate a
patient's genetic material to treat or cure disease,
often by introducing new genes or replacing defective
genes with a healthy copy. Delivering the
updated genetic material containing the correction
is often achieved with viral vectors. The development
of gene therapies can be constrained
by the need for large-scale viral production. The
same can be said for the development of antiviral
vaccines. Although producing large amounts of
viruses is critical for delivering these therapies to
many patients, relatively little work has been done
to improve viral production capacity of the most
common cell lines used in virus production.
In the second chapter of this eBook, we present
a novel solution: CAR-T target luciferase reporter
cells.10,11
These cells, derived from a variety of
highly malignant liquid and solid cancers, facilitate
analysis of cytotoxicity through bioluminescence.
They also endogenously express CD19, CD20, or
HER2, making them a physiologically relevant in
vitro tool for testing CAR-T cell function and efficacy,
eliminating the requirement for donor-derived
cells-and the variability and irreproducibility that
inevitably results from their use.
5
eBook: Cell and Gene Therapy

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