Antibody Screening Solutions Made Easy - 16

Antibody Screening Solutions Made Easy * Advances in Discovery and Screening of Therapeutic Antibodies

therapy is chimeric antigen receptor (CAR) T-cell
therapy. CAR T-cell therapy utilizes monoclonal
antibodies to engineer immune cells, providing
target recognition of cancer.
Third, bispecific therapeutic antibodies can be
engineered to recognize two different epitopes,
such as one on a T cell and another on a cancer
cell. Bispecific antibodies bring T cells and cancer
cells together, assisting T cells in recognizing and
killing cancer.
Traditionally, monoclonal antibodies were made
by injecting mice with an antigen, harvesting
their spleens and making hybridomas by fusing
the spleen cells with human cells. "The next step,
in systems past, was to immobilize an antigen
of interest on the bottom of an ELISA (enzymelinked immunosorbent assay) plate and screen for
antibodies that bind," notes Dr. Duensing.
Unfortunately, certain proteins, such as those
found in the cell membrane, suffer upon immobilization. Once attached to the bottom of ELISA
plates these proteins often become denatured
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during the purification process. The antigen's
secondary and tertiary structure can be lost when
the antigen is no longer in its native state; this is
especially true for proteins normally inserted
into the cell membrane. Screened antibodies
that reacted well in an ELISA assay often
cannot accurately identify native proteins.
"Conventionally, the whole approach had to be
carried out in a stepwise fashion. It was extremely
labor and time intensive. Current approaches apply cell-based assays and the ability to multiplex
assays within the same plate. This offers a biologically relevant screen as well as saving labor and
time," communicates Dr. Duensing.
Cells expressing the target antigen can be used
in multiplexed screens with the Intellicyt's iQue
platform. Target proteins expressed in their native
state yield biologically relevant results. Clients
can improve their screening results by running
multiplex assays that include a control cell line
that does not express the target antigen.
Additionally, researchers use multiplexed assays to

screen for antibodies that bind to a target antigen
from different species. When the antibody development process moves to downstream nonhuman, whole-animal models, efficacy and toxicity
results are more pertinent than for antibodies only
known to bind human forms of an antigen.

Automating Antibody Internalization
"A key question in antibody drug discovery is the
extent and rate of internalization of the candidate
antibody into cells," remarks Derek (Del) Trezise,
Ph.D., senior director of Essen BioScience, a
Sartorius company. "This characteristic affects the
efficacy, safety, and pharmacodynamic properties."
"In the past, internalization assays were restricted
to a few candidate antibodies that were far progressed down the discovery path," he continues.
"Significant investments of time and energy were
already expended. Leveraging new approaches
like the IncuCyte® live-cell analysis platform permits companies to rapidly generate this information further upstream to enable earlier and more
informed decisions."

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Antibody Screening Solutions Made Easy

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