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Combinatorial Phage Antibody Libraries
Combinatorial Antibody Library
A large ensemble of antibody molecules expressed in a given vector, generally derived
by the independent cloning of single heavy- and light-chain genes in the vector.
Panning
An afFnity-based selection procedure for the isolation of an antibody phage with
speciFcity for a desired antigen or epitope.
Phage Display
The expression of proteins or peptides on the surface of a Flamentous bacteriophage.
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Evolutionary pressure has driven the need for immune systems of considerable
complexity and Fnesse. Indeed, to function efFciently, host immunity must be equal
to the diversity and ingenuity of organisms that threaten the well-being of the animal.
Antibody-mediated immune defense plays a pivotal role in this process. This article
discusses the development and application of combinatorial antibody libraries, an
approach to the generation of human monoclonal antibodies that began in the
early 1990s and has generated increasing interest, both academic and commercial,
ever since.
1
Overview
Antibody molecules are characterized by
their ability to engage in high-afFnity in-
teractions of narrowly deFned speciFcity.
These properties make antibodies appeal-
ing as potential therapeutic agents. There
are in fact several examples in which
serum antibody preparations, derived from
individuals with high serum titers against
particular antigens or pathogens, have
proven useful in the clinic. ±or exam-
ple, the incidence of hemolytic disease
of the newborn has decreased dramat-
ically in countries where anti-rhesus D
prophylaxis is practiced. There are, how-
ever, a number of problems inherent to
hyperimmune serum that prevent its wider
application. ±irst, it is practically available
only in limited supply. Second, because it
is a blood product, hyperimmune serum
cannot be guaranteed completely safe for
the recipient. Outbreaks of hepatitis in
Ireland and Eastern Europe, traced back
to contaminated batches of anti-rhesus
D hyperimmune sera, have underlined
this concern. Most importantly, however,
serum preparations are an extremely inef-
Fcient way of delivering useful antibodies.
Even in the most favorable circumstances,
only a small proportion of the antibody
in such sera will possess the desired
speciFcity.
The arrival of hybridoma technology pre-
sented the opportunity to produce large-
scale quantities of rodent monoclonal
antibodies of a desired speciFcity, but
these antibodies elicit a strong immune
response in humans and have proven to
be of limited use for therapy. Moreover,
the generation of human monoclonal
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