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Researchers find cause of severe allergic reaction to cancer drug
Date:3/12/2008

y controlling the growth of cancer cells.

Upon reviewing the scientific literature, the research team was intrigued by the unusual geographic distribution of patients with anaphylaxis. For example, 22 percent of patients treated with cetuximab in Tennessee and North Carolina had anaphylactic reactions and even higher rates and clusters of cases were reported from regions of Arkansas, Missouri and Virginia. In contrast, less than 1 percent of patients receiving cetuximab in the Northeast region of the United States suffered such reactions.

Anaphylactic reactions are typically triggered by immunoglobulin E (IgE) antibodies, which the immune system produces after being sensitized by prior exposure to an allergen, a normally harmless substance that in some people causes an abnormal immune response. But when Dr. Platts-Mills and his collaborators further reviewed the clinical data, they came across another unusual finding. Anaphylactic reactions in these individuals had occurred within minutes of their first exposure to cetuximab, suggesting that the patients had already been primed to respond to cetuximab.

The researchers then hypothesized that these patients had pre-existing IgE antibodies that cross-reacted with cetuximab and that these IgE antibodies were directed against a specific sugar molecule present on cetuximab. This hypothesis was derived, in part, from knowledge that all people develop natural antibodies to sugars found on foods, bacteria and viruses, although such antibodies are of a non-IgE class, called IgM.

To test their hypothesis, Dr. Platts-Mills and his colleagues analyzed the antibodies present in serum of 538 individuals. They developed a technique for measuring IgE antibodies to cetuximab and, in further experiments, proved that the IgE antibodies were directed against sugar molecules on cetuximab.

The 538 serum samples included pre-treatment samples taken from 76 cetuximab-treated cancer patients
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Contact: Sitara Maruf
marufs@niaid.nih.gov
301-402-1663
NIH/National Institute of Allergy and Infectious Diseases
Source:Eurekalert

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