Aglycosylated full-length IgG antibodies: Steps toward next-generation immunotherapeutics

Man Seok Ju, Sang Taek Jung

Research output: Contribution to journalReview articlepeer-review

48 Citations (Scopus)

Abstract

Albeit the removal of Asn297 glycans of IgG perturbs the overall conformation and flexibility of the IgG CH2 domain, resulting in the loss of Fc-ligand interactions and therapeutically critical immune effector functions, aglycosylated full-length IgG antibodies are nearly identical to the glycosylated counterparts in terms of antigen binding, stability at physiological or low temperature conditions, pharmacokinetics, and biodistribution. To bypass the drawbacks of glycosylated antibodies that include glycan heterogeneity and requirement of high capital investment for biomanufacturing, aglycosylated antibodies have been developed and several are under clinical trials. Comprehensive cellular and bioprocess engineering has enabled to produce highly complex aglycosylated IgGs in a simple bacterial cultivation with comparable production level as that of mammalian cells. Moreover, extensive engineering of aglycosylated Fc has converted the aglycosylated IgG antibodies into a new class of effector functional human immunotherapeutics.

Original languageEnglish
Pages (from-to)128-139
Number of pages12
JournalCurrent Opinion in Biotechnology
Volume30
DOIs
Publication statusPublished - 2014 Dec
Externally publishedYes

Bibliographical note

Funding Information:
Research on aglycosylated antibody engineering has been supported by the Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Science, ICT and Future Planning ( 2013R1A1A1004576 ), and a grant from the National R&D Program for Cancer Control, Ministry of Health and Welfare, Republic of Korea (1420160). Man-Seok Ju was supported by BK21 Plus from the Ministry of Education of Korea . We thank Dr. Tae Hyun Kang for his valuable comments on this manuscript.

ASJC Scopus subject areas

  • Biotechnology
  • Bioengineering
  • Biomedical Engineering

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