Page 9 - Revista FRONTAL Edição Especial iMed 12.0

KEYNOTE LECTURE

protein and those other molecules. In an year later he was Elected by the Amer- Phage display of antibody libraries
this way, large libraries of proteins can ican Association for the Advancement of has become a powerful method for both
be screened and amplified in a process Science (AAAS). Later, in 2007, he won the studying the immune response as well
called in vitro selection, which is analo- American Society for Microbiology Pro- as a method to rapidly select and evolve
gous to natural selection. mega Biotechnology Research Award. human antibodies for therapy. This An-
The most common bacteriophages Finally, George P. Smith was awarded tibody libraries displaying millions of
used in phage display are M13 and fd fila- the 2018 Nobel Prize in Chemistry for this different antibodies on phage are often
mentous phage. work in phage display, sharing his prize used in the pharmaceutical industry to
This technique was first described by with Greg Winter and Frances Arnold. isolate highly specific therapeutic an-
George P. Smith in 1985 when he demon- This new technology has several useful tibodies, that are developed into anti-
strated the display of peptides on filamen- applications. It can be used in the deter- body drugs primarily as anti-cancer or
tous phage (long, thin viruses that infect mination of interaction partners of a pro- anti-inflammatory therapeutics. One
bacteria) by fusing the virus's capsid pro- tein so that the mechanisms and faction of the most successful was adalimum-
tein to one peptide out of a collection of of the studied protein can be found. It is ab, discovered by Cambridge Antibody
peptide sequences. This displayed the also a widely used method for protein en- Technology as D2E7 and developed and
different peptides on the outer surfaces gineering, drug discovery, and in search- marketed by Abbott Laboratories. Adali-
of the collection of viral clones, where the ing for protein-DNA interactions, using mumab, an antibody to TNF alpha, was
screening step of the process isolated the specially-constructed DNA libraries with the world's first fully human antibody.
peptides with the highest binding affinity. randomized segments. In addition to his valuable contribution
Three years later, Stephen Parmley Moreover, it can be a helpful tool to to science, George Smith is also an advo-
and George Smith described biopanning find new ligands (enzyme inhibitors, re- cate for equal rights for Palestinians and
for affinity selection. ceptor agonists and antagonists) to tar- Israeli Jews in their common homeland,
In 1990, Jamie Scott and George Smith get proteins and to determine tumor and a strong supporter of the Boycott, Di-
explained the process of creation of large antigens (helping in diagnosis and thera- vestment and Sanctions movement.
random peptide libraries displayed on fil- peutic targeting). Actually, phage display On the topic of religion, Smith is quot-
amentous phage. has been recently used in the context of ed as saying "I'm not religious or Jewish by
This technology was further developed cancer treatments- such as the adoptive birth. But my wife is Jewish and our sons
and improved by three research groups: cell transfer approach. In these cases, are bar-mitzvahed, and I'm very engaged
the Laboratory of Molecular Biology with phage display is used to create and select with Jewish culture and politics."
Greg Winter and John McCafferty, The synthetic antibodies that target tumor
Scripps Research Institute with Richard surface proteins. These are made into
Lerner and Carlos Barbas and the German synthetic receptors for T-Cells collected
Cancer Research Center with Frank Bre- from the patient that are used to combat
itling and Stefan Dübel. The main goal was the disease.
the display of proteins such as antibodies Competing methods for in vitro pro-
for therapeutic protein engineering. tein evolution include yeast display,
In 2000, George Smith became Uni- bacterial display, ribosome display, and
versity of Missouri Curators' Professor, and mRNA display.

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