By Dr. Larry Chiaramonte
Allergy shots or subcutaneous immunotherapy [SCIT] have been given for over a century or so. Everyone who has ever gotten a shot of any kind wishes there were alternatives. Allergy shots are exceptionally annoying. The patient, or patient and mom or dad, waits for the doctor or nurse, gets stuck, and then has to hang around for half an hour in the event of an adverse reaction. Can’t they invent a pill instead? Can’t I take them at home? Must this go on for 3-5 years? Sadly for all these disgruntled patients, shots have long been the closest thing we have to a cure for allergies, and they pay off both in better quality of life and money. (By coincidence, a new study suggests that patients don’t care very much how many shots they get as long as they work.)
The dream of pills is partially fulfilled with daily drops under the tongue [SLIT] as given in Europe. I recently wrote about three products have been recently approved by the FDA for sublingual immunotherapy [SLIT] in the US. For many practical reasons the general opinion is that these will have little impact for sometime on the treatment of asthma and allergy.
But that wish for a drastically shorter course of treatment is also on the horizon in the form of Synthetic Peptide Immuno-Regulatory Epitopes (SPIREs), which represent a totally new class of allergy treatment. These synthetic peptides containing the epitopes of allergens—i.e. the parts of proteins that actually provoke the immune response–offer the potential of a short course of immunotherapy with minimal side effects that treats the underlying allergic disease. Only four injections are required for a total course of immunotherapy. They are made by a British company called Circassia, part of a product called ToleroMune®.
Circassia is conducting multi-center clinical trials in the U.S. for cat, dust mite, grass and ragweed. The cat allergen is in phase III. Our contributor Dr. Harold Nelson is directing the clinical trials.
How Synthetic Peptide Immuno-Regulatory Epitopes. [SPIRES] work:
Normally an antigen-processing cell [APC] presents the antigen and stimulates one of three types of T cells, a CD4 T or either H1 or H2 helper cells. H1 stimulates the formation of IgG antibody, while an H2 cell stimulates the formation of an IgE antibody though a B cell. In addition, the APC may stimulate naïve T cells to differentiate into regulatory T cells (T-reg), which have an inhibitory effect on various cells involved in triggering the allergic response.
When the APCs process SPIREs instead of normal allergens, it will stimulate naïve T cells to differentiate into regulatory T cells (T-reg), which have an inhibitory effect on various cells involved in triggering the allergic response. T-regs inhibit mast cells from releasing their toxic soup of histamine and other mediators from being released. This effectively blocks the inflammatory cascade of sneezing, runny nose, and itchy eyes.
The goal of these products is to provoke the CD4 H1 T cell to stimulate IgG antibody production to inhibit allergy without stimulating IgE production or activation. Regulatory T cells also stop T-helper (Th) cells (Th1 and Th2) from secreting inflammatory molecules that irritate the lungs and airways, leading to coughing, mucus secretion and wheezing. The peptides do not cross-link IgE antibodies on mast cells, which avoids the need to gradually increase doses over a long period. The hope is that tolerance to allergens could be achieved with just four shots over a 12-week period.
Cat lovers will particularly welcome the development of Cat-SPIRE, which is the most advanced of these treatments and is currently undergoing the final phase of clinical testing. A number of phase II studies showed that a short course of treatment safely reduced patients’ symptoms after two years after the start of the study, despite no further treatment. The treatment began phase III testing in October 2012.
House dust mite-SPIRE contains synthetically manufactured peptides identified in the key allergen. House Dust Mite (HDM)-SPIRE, Grass-SPIRE and Ragweed-SPIRE have also successfully completed proof-of-concept phase IIb clinical studies.
(Note: As in so many other avenues of allergy research, there’s an air of “everything old is new again” in this current research. Forty years ago a group out of Hopkins prepared what they called an allergoid or a protein antigen that was modified with the objective to stimulate IgG antibody production without stimulating IgE production or activation. The natural antigen was polymerized by application of glutaraldeide, formaldehyde or microbial transglutaminases. Unfortunately these never made it to market. Marsh DG, Lichtenstein LM, Campbell DH. Studies on “allergoids” prepared from naturally occurring allergens. I. Assay of allergenicity and antigenicity of formalinized rye group I component. Immunology 1970; 18:705-22.)