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Related Experiment Videos

Aglycosylated chimeric mouse/human IgG1 antibody retains some effector function.

H Dorai1, B M Mueller, R A Reisfeld

  • 1Abbott Biotech, Inc., Needham Heights, MA 02194.

Hybridoma
|April 1, 1991
PubMed
Summary

Aglycosylated human IgG1 antibodies lack antibody-dependent cell-mediated cytotoxicity (ADCC) but retain complement-dependent cytotoxicity (CDC). Serum half-life and biodistribution remain comparable to native antibodies.

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Area of Science:

  • Immunology
  • Biochemistry
  • Molecular Biology

Background:

  • N-linked glycosylation is crucial for the function of many proteins, including antibodies.
  • The role of glycosylation in the effector functions of human IgG1 antibodies is complex and not fully understood.

Purpose of the Study:

  • To investigate the impact of removing the N-linked glycosylation site on the effector functions of human IgG1 antibodies.
  • To compare the effector functions, serum half-life, and biodistribution of aglycosylated IgG1 antibodies with their native counterparts.

Main Methods:

  • Site-directed mutagenesis was used to eliminate the N-linked carbohydrate attachment site in human IgG1 antibodies.
  • Effector functions, including antibody-dependent cell-mediated cytotoxicity (ADCC) and complement-dependent cytotoxicity (CDC), were assessed.

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  • Serum half-life and biodistribution were evaluated in mice.
  • Main Results:

    • Aglycosylated human IgG1 antibodies completely lost antibody-dependent cell-mediated cytotoxicity (ADCC) activity.
    • A significant level of complement-dependent cytotoxicity (CDC) activity was retained by the aglycosylated antibodies.
    • Serum half-life and biodistribution in mice were comparable between aglycosylated and native IgG1 antibodies.

    Conclusions:

    • N-linked glycosylation critically affects the ADCC activity of human IgG1 antibodies.
    • CDC activity is largely independent of N-linked glycosylation for human IgG1 antibodies.
    • Aglycosylation does not significantly alter the in vivo pharmacokinetics of human IgG1 antibodies.