Integrated clinical experience with tolerogenic peptides.
More than 2,000 patients have been dosed in the clinical development programs for Allervax Cat and Ragweed products in North America, Europe and Japan. Two peptides derived from Fel d 1 and three peptides derived from Amb a 1 were selected for clinical development following T cell epitope mapping of these major allergens. Clinical activity has been demonstrated in several dose regimens containing 75 and 750 microg of each component peptide given in 4-6 doses over 2-4 weeks. Greater activity has been seen with higher doses. Immediate hypersensitivity to treatment peptides is rarely seen and can be avoided through patient screening. A putative pathway resulting in histamine-mediated but IgE-independent allergic symptoms, similar in nature and severity to natural allergen exposure, has been identified in association with treatment. These manifestations are more pronounced in cat than ragweed allergy and are consistent with the respective diseases. When desired, the symptoms may be ameliorated with administration of H1 blockers prior to symptom appearance. The seasonal rise in allergen-specific IgE is blunted in association with therapy. Antigen-specific antibody levels (IgE and IgG), T cell primary proliferation and immediate skin test sensitivity will be followed in longer-term studies.
Nicodemus
C
C
ImmuLogic Pharmaceutical Corporation, Waltham, Mass. 02154, USA.
Philip
G
G
Jones
N
N
Hirani
S
S
Norman
P
P
D000485:Allergens / Q000276:immunology*; D000818:Animals; D002415:Cats / Q000276:immunology*; D006023:Glycoproteins / Q000276:immunology*; D006633:Histamine Antagonists / Q000627:therapeutic use; D006801:Humans; D006967:Hypersensitivity / Q000628:therapy*; D013601:T-Lymphocytes / Q000276:immunology
D000485:Allergens; D006023:Glycoproteins; D006633:Histamine Antagonists; C059296:Fel d 1 protein, Felis domesticus