1: Effects of a novel drug - from animal to human

Novel drug (peptide) induced signs of histamine release in skin and subcutis in dogs following iv treatment in a pre-clinical study. Could this assumption be verified by ex vivo testing in human skin?

Conclusion:

The present ex vivo microdialysis study in human skin slices confirmed the observations in dogs, indicating a histamine releasing potential of compound at a concentration which is 10 to 100 times higher than therapeutic concentrations. These results supported FDA approval of the drug to be tested in humans.

2: Testing monoclonal antibodies for histamine releasing activity

Company developing monoclonals to treat inflammatory/autoimmune diseases:

If the monoclonal is directed against a specific receptor shared by mast cells or basophils then the antibody is tested routinely in human basophils and ex vivo human skin for histamine releasing activity.

Example:

Novel anti C5a receptor antibody was tested for histamine releasing activity in human basophils and ex-vivo human skin. No histamine release was found indicating that the compound had no allergy like side effects.

3: Mechanism of allergy like side effects in a phase 3 study

Basophils from clinical trial subjects showing allergy like side effects were tested for histamine release, but showed no sign of sensitization to the drug demonstrated by lack of histamine release.

Furthermore the compound was tested for histamine release activity in healthy ex vivo human skin and showed no release.

Conclusion:

The compound have no impact on mast cells or basophils – neither IgE nor non-IgE-mediated. It is therefore less likely that the compound induces anaphylaxis. Mechanism of side effects is still unknown.

4: Detection of rare allergens in processed food

Company wish to test any remaining allergenic activity in a processed food ingredient.

The biological activity of rare allergens in processed food were tested by basophil histamine release.

Sera from highly reactive allergics were used to passively sensitize basophils from healthy donors. Then sensitized cells were challenged with processed food and showed no sign of allergen specific biological activity

5: Detection of biological activity of allergens intended for use in immunotherapy

Allergen producer wanted an assessment of the biological activity of newly developed recombinant or purified allergens.

Biological activity were investigated by sensitizing healthy donor basophils with highly reactive sera. Subsequent histamine release was determined after activation with the allergens. The results were used for the biological standardization and included in the final characterization of the allergens.