New approaches to immunotherapy

Author: V. Dimov, M.D., Allergist/Immunologist and Assistant Professor at University of Chicago
Reviewer: S. Randhawa, M.D., Allergist/Immunologist and Assistant Professor at NSU

Allergen immunotherapy was introduced by Leonard Noon 100 years ago and is the only disease-modifying treatment for allergic individuals (Allergy, 2012).


Mechanisms of allergen-specific immunotherapy (click to enlarge the image).

Novel approaches to immunotherapy

- Sublingual immunotherapy (SLIT)
- Peptide-based immunotherapy
- CpG-enhanced immunotherapy
- Anti-IgE and immunotherapy
- Recombinant allergen vaccines
- Epicutaneous allergen-specific immunotherapy. Skin patches coated with allergens to treat hay fever - check the caveats too listed by WSJ and JACI, 2011.

SLIT

Interesting fact: The longest human tongue ever recorded was that of Stephen Taylor and measures 9.8 centimetres (3.86 in). The longest tongue for a female is that of Annika Irmler at 7 centimetres (2.76 in).

The World Health Organization concluded that SLIT was a viable alternative to SCIT in 1998.

Practical aspects of SLIT

- Self-administered by patients
- Soluble tablets or drops
- Sublingual-swallow: keep under the tongue for 1-2 min, then swallow. Contact time with the oral mucosa is critical to the effectiveness of SLIT - if the allergen is immediately swallowed, there are negligible clinical effects.
- Dose of allergen greater than for SCIT (3-300 times higher)
- Administration schedule and amount of allergen vary, depending on the manufacturer
- Amount of allergen given during a course of SLIT is higher than in SCIT: there is a bild-up phase (very rapid), followed by a maintenance phase

Efficacy of SLIT in allergic rhinitis

The magnitude of clinical efficacy ranged from 20-60% reduction of symptoms. House dust mite (HDM) SLIT was less effective, but results were comparable to SCIT. For HDM, duration of treatment seems to be crucial - treatments that lasted longer than 24 months had positive results.

Clinical safety of SCIT vs. SLIT

Safety of SCIT

Systemic reactions occur in 0.05-0.6% of doses administered. Rare fatalities have been reported.

Safety of SLIT

No life-threatening adverse events reported since 1986. Most common adverse effects include oral/sublingual itching, stomachache, and nausea. No increased risk in patients with oral allergy syndrome.

Sublingual immunotherapy is safe during pregnancy, it is also safe when initiated for the first time in pregnancy (study) (Allergy, 2012).

CpG-enhanced immunotherapy

Bacterial DNA contains unmethylated CpG di-nucleotides (CpG motifs) that act as a danger signal to the vertebrate immune system and trigger protective innate and acquired immune responses.

CpGs work through toll-like receptor 9 (TLR-9) to activate monocytes, dendritic cells, B cells, and NK cells. CPGs promote Th1 and inhibit Th2 response (similar to allergen-specific SCIT). TLR9 and MyD88 play central role in protective immunity to malaria http://goo.gl/VVF07

The immune stimulatory activity of bacterial DNA can be mimicked by synthetic oligodeoxynucleotides containing CpG motifs. They can be added to a vaccine or linked to an
antigen to greatly boost the immune response.

Anti-IgE (omalizumab (Xoliar) and immunotherapy

The combination anti-IgE and allergen immunotherapy might offer advantages that
neither method can provide separately. Anti-IgE administered during the induction phase
of immunotherapy might reduce the risk of IgE-mediated anaphylaxis.

References

Allergen-specific immunotherapy for respiratory allergies: From meta-analysis to registration and beyond. JACI, 2010.

Related reading

Immunotherapy in Asthma - 11-page Medscape review http://goo.gl/KUAcA

Sublingual immunotherapy is an extremely complex issue in the U.S. AAAAI http://goo.gl/wVOKr

Timothy grass allergy immunotherapy tablets safe and effective in American children with allergic rhinitis http://goo.gl/tsKL4

Efficacy and safety of timothy grass allergy immunotherapy tablet treatment in North American adults - it works. http://goo.gl/ePOFG

Epicutaneous allergen administration: is this the future of allergen-specific immunotherapy? Allergy, 2011.

Published: 06/27/2010

Updated: 03/15/2012