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Crit Rev Biotechnol. 2018 May;38(3):394-408. doi: 10.1080/07388551.2017.1357002. Epub 2017 Aug 8.

Monoclonal antibodies: technologies for early discovery and engineering.

Kennedy PJ1,2,3,4, Oliveira C1,3, Granja PL1,2,4,5, Sarmento B1,2,6.

Author information

1
a i3S - Instituto de Investigação e Inovação em Saúde , Universidade do Porto , Porto , Portugal.
2
b INEB - Instituto de Engenharia Biomédica , Universidade do Porto , Porto , Portugal.
3
c IPATIMUP - Instituto de Patologia e Imunologia Molecular da Universidade do Porto , Porto , Portugal.
4
d ICBAS - Instituto de Ciências Biomédicas Abel Salazar , Universidade do Porto , Porto , Portugal.
5
e Departmento de Engenharia Metalúrgica e de Materiais , FEUP - Faculdade de Engenharia da Universidade do Porto , Porto , Portugal.
6
f CESPU , Instituto de Investigação e Formação Avançada em Ciências e Tecnologias da Saúde & Instituto Universitário de Ciências da Saúde , Gandra , Portugal.

Abstract

Antibodies are essential in modern life sciences biotechnology. Their architecture and diversity allow for high specificity and affinity to a wide array of biochemicals. Combining monoclonal antibody (mAb) technology with recombinant DNA and protein expression links antibody genotype with phenotype. Yet, the ability to select and screen for high affinity binders from recombinantly-displayed, combinatorial libraries unleashes the true power of mAbs and a flood of clinical applications. The identification of novel antibodies can be accomplished by a myriad of in vitro display technologies from the proven (e.g. phage) to the emerging (e.g. mammalian cell and cell-free) based on affinity binding as well as function. Lead candidates can be further engineered for increased affinity and half-life, reduced immunogenicity and/or enhanced manufacturing, and storage capabilities. This review begins with antibody biology and how the structure and genetic machinery relate to function, diversity, and in vivo affinity maturation and follows with the general requirements of (therapeutic) antibody discovery and engineering with an emphasis on in vitro display technologies. Throughout, we highlight where antibody biology inspires technology development and where high-throughput, "big data" and in silico strategies are playing an increasing role. Antibodies dominate the growing class of targeted therapeutics, alone or as bioconjugates. However, their versatility extends to research, diagnostics, and beyond.

KEYWORDS:

Monoclonal antibody; antibody biology; antibody engineering; antibody selection strategy; in silico antibody; in vitro display technology

PMID:
28789584
DOI:
10.1080/07388551.2017.1357002
[Indexed for MEDLINE]

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