Alpha-Gal-containing biologics and anaphylaxis.

Area of Science:

• Immunology
• Allergology
• Pharmacology

Background:

• Cetuximab, an EGFR-targeting monoclonal antibody, is used for colorectal and head and neck cancers.
• Anaphylaxis is a severe adverse reaction to cetuximab.
• The cause of cetuximab-induced anaphylaxis is linked to anti-oligosaccharide IgE antibodies.

Purpose of the Study:

• To investigate the cause of cetuximab-induced anaphylaxis.
• To identify the specific allergen responsible for cetuximab allergy.
• To explore the cross-reactivity between cetuximab allergy and mammalian meat allergy.

Main Methods:

• Investigated IgE antibodies targeting galactose-α-1,3-galactose (α-Gal) oligosaccharide.
• Examined cross-reactivity with mammalian meat containing α-Gal.
• Assessed the role of tick bites in α-Gal sensitization.
• Evaluated the utility of α-Gal-specific IgE testing.

Main Results:

• The primary cause of cetuximab anaphylaxis is IgE antibodies specific to the α-Gal oligosaccharide found on the antibody's mouse-derived portion.
• Patients allergic to cetuximab also react to mammalian meat due to cross-reactivity with α-Gal.
• Tick bites are identified as a significant factor in sensitization to α-Gal.

Conclusions:

• Oligosaccharides can be major IgE epitopes in anaphylaxis.
• Cross-reactivity between cetuximab and mammalian meat allergies is mediated by the α-Gal epitope.
• Tick bites are a key sensitizing event for α-Gal allergy.
• α-Gal-specific IgE testing is essential for identifying patients at risk of cetuximab-induced anaphylaxis.