Why Drug Developers Choose IgG4 for Monoclonal Antibodies? – Illiasul Ibad
Illiasul Ibad, Rheumatologist at Christian Medical College, posted on X:
”1․ Why are many therapeutic monoclonal antibodies built on the IgG4 framework?
2․ Understand basics
Biology of IgG4
• Least abundant IgG subclass
• Very weak complement activation
• Poor interaction with Fc receptors → almost no ADCC
Translation: IgG4 can block targets without collateral tissue damage.
3․ Fab-arm exchange
Natural IgG4 can swap half its arms → becomes “functionally monovalent.”
Good for tolerance in nature, but bad for drug stability.
Solution: scientists engineered the S228P mutation → no swapping, molecule stays stable.
4․ Why drug developers love IgG4
• Precise blocking, not killing
• Low inflammation risk
• Engineered stability
• Safe for long-term therapy
That’s why IgG4 is the backbone of modern antibody medicines – quiet, stable, effective.”
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