Advances in immunotherapy for allergies have increased safety and effectiveness

Casale and Stokes take a look at new technologies and experimental therapies developed to improve on the standard approach of subcutaneous injection of increasing concentrations of allergens (SCIT) in this month’s issue (J Allergy Clin Immunol 2011;127:8-15). They discuss omalizumab add-on therapy to conventional SCIT and report on studies in which omalizumab was administered concurrently and prior to initiation of SCIT. Omalizumab plus SCIT showed significant reduction in allergic rhinitis symptoms, and less use of rescue medication compared to SCIT alone. When omalizumab was given as pre-treatment to SCIT, both allergic rhinitis and allergic asthma subjects had fewer severe reactions and more subjects were able to achieve target maintenance dose than subjects receiving placebo plus SCIT.

The authors continue with recent efforts to mobilize mitigating Th1 responses through Toll-like receptor (TLR) agonists and CpG immunostimulatory responses. Combined allergen and TLR therapy is reported to provide significant improvements in rhinitis symptoms and medication use in both adults and children. They also discuss effectiveness associated with bonding immunostimulatory CpG sequences with ragweed allergen to influence T cell responses toward Th1 dominance and reduced eosinophilia; however, clinical impact was minimal. Engineering the allergen and CpG sequences, as well as CpG sequences alone, into virus-like particles provided significantly greater improvements in symptoms and immunologic markers.

Casale and Stokes cover the use of T-cell derived peptides in the treatment of allergies including cat allergy and bee venom allergy. They describe increased benefit and safety of SCIT therapy with newer preparations of Fel d 1 peptides, and early impressive results with Api m 1 and phospholipase A2.

Different routes of administration are also reviewed by the authors such as intranasal and intrabronchial, focusing on escalating oral and sublingual (SLIT) therapies. They report encouraging results from oral desensitization/tolerance studies for subjects with food allergies, which included decreased inflammation markers, decreased specific IgE, increased specific IgG, and achievement of tolerance in a majority of subjects. Results from SLIT therapy trials have been positive as well. SLIT clinical trials for grass and ragweed allergies have shown efficacy in subjects with seasonal allergic rhinitis, and there are positive results noted for other allergens in seasonal allergic rhinitis and allergic asthma.

In conclusion, the authors comment that adjunct omalizumab therapy clearly improves safety and TLR agonists are more effective for shifting to Th1 response. They are optimistic about the future of immunotherapy, although they feel that with the rapid evolution in new technology and increased knowledge of the immune system, how immunotherapy will be used in the future will be substantially different than what is occurring today.