Boosting therapeutic potency of antibodies by taming Fc domain functions

Tae Hyun Kang, Sang Taek Jung

Research output: Contribution to journalReview articlepeer-review

89 Citations (Scopus)

Abstract

Monoclonal antibodies (mAbs) are one of the most widely used drug platforms for infectious diseases or cancer therapeutics because they selectively target pathogens, infectious cells, cancerous cells, and even immune cells. In this way, they mediate the elimination of target molecules and cells with fewer side effects than other therapeutic modalities. In particular, cancer therapeutic mAbs can recognize cell-surface proteins on target cells and then kill the targeted cells by multiple mechanisms that are dependent upon a fragment crystallizable (Fc) domain interacting with effector Fc gamma receptors, including antibody-dependent cell-mediated cytotoxicity and antibody-dependent cell-mediated phagocytosis. Extensive engineering efforts have been made toward tuning Fc functions by either reinforcing (e.g. for targeted therapy) or disabling (e.g. for immune checkpoint blockade therapy) effector functions and prolonging the serum half-lives of antibodies, as necessary. In this report, we review Fc engineering efforts to improve therapeutic potency, and propose future antibody engineering directions that can fulfill unmet medical needs.

Original languageEnglish
Article number138
JournalExperimental and Molecular Medicine
Volume51
Issue number11
DOIs
Publication statusPublished - 2019 Nov 1

Bibliographical note

Funding Information:
This work was supported by grants from the Basic Science Research Programs (2019R1F1A1059834 and 2019R1A4A1029000), the Bio & Medical Technology Development Program (2017M3A9C8060541), and the Pioneer Research Center Program (2014M3C1A3051460) through the National Research Foundation of Korea funded by the Ministry of Science and ICT.

Publisher Copyright:
© 2019, The Author(s).

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Medicine
  • Molecular Biology
  • Clinical Biochemistry

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