Trends in therapeutic antibody affinity maturation: From in-vitro towards next-generation sequencing approaches

Immunol Lett. 2019 Aug:212:106-113. doi: 10.1016/j.imlet.2019.06.009. Epub 2019 Jun 24.

Abstract

Current advances in antibody engineering driving the strongest growth area in biotherapeutic agents development. Affinity improvement that is mainly important for biological activity and clinical efficacy of therapeutic antibodies, has still remained a challenging task. In the human body, during a course of immune response affinity maturation increase antibody activity by several rounds of somatic hypermutation and clonal selection in the germinal center. The final outputs are antibodies representing higher affinity and specificity against a particular antigen. In the realm of biotechnology, exploring of mutations which improve antibody affinity while preserving its specificity and stability is an extremely time-consuming and laborious process. Recent advances in computational algorithms and DNA sequencing technologies help researchers to redesign antibody structure to achieve desired properties such as improved binding affinity. In this review, we briefly described the principle of affinity maturation and different corresponding in vitro techniques. Also, we recapitulated the most recent advancements in the field of antibody affinity maturation including computational approaches and next-generation sequencing (NGS).

Keywords: Affinity maturation; In silico; Mutagenesis; NGS.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Antibodies / genetics*
  • Antibodies / immunology
  • Antibodies / metabolism
  • Antibodies / therapeutic use
  • Antibody Affinity / genetics*
  • Antigens / immunology
  • Antigens / metabolism
  • Clonal Selection, Antigen-Mediated / genetics
  • Clonal Selection, Antigen-Mediated / immunology
  • Computational Biology / methods*
  • High-Throughput Nucleotide Sequencing*
  • Humans
  • Mutagenesis / immunology
  • Mutation
  • Protein Engineering / methods*

Substances

  • Antibodies
  • Antigens