Allergen-Specific Human Monoclonal IgG Antibodies for Use in Passive Allergy Immunotherapy.

Abstract

The last decades have shown the number of subjects developing allergic rhinitis (AR), allergic asthma (AA), atopic dermatitis (AD), and food allergy rose continuously worldwide. To cure these allergic diseases, allergen-specific immunotherapy (AIT) represents the unique treatment capable of providing clinical outcomes through the induction of long-term immunological tolerance. Despite proven efficacy, the duration of treatment, AIT-associated side effects, and the difficulty in identifying potential responders by diagnosis lead to poor patient compliance. Clinical investigations evidenced the role of blocking IgG antibodies induced by AIT in long-term tolerance. These observations suggested that passive allergy immunotherapy (PAIT) with low doses of allergen-specific blocking IgG antibodies represents an elegant alternative to frequent administrations of allergen extracts. Tremendous technological progress in the discovery/production of fully human monoclonal antibodies (mAbs) with very low immunogenicity has been made in the last decades, and these therapeutic antibodies revolutionised the treatment of cancers or infectious diseases. The recent advances in the isolation of rare allergen-specific IgE+ B cells and the generation of human antibodies in transgenic mice made possible the production of human monoclonal blocking antibodies against any allergen, sharing the same affinity with the corresponding naturally occurring IgE. This comprehensive review will describe the first promising preclinical and clinical data obtained with antibody cocktails targeting several IgE epitopes to some key single allergens. PAIT is safe and effective for the downregulation of the allergic response. Compared with conventional extract-based AIT, the positive outcomes could require much less dosing.