Future forms of immunotherapy - what is practical?

Allergic respiratory diseases affect 15% of the US population. Allergen immunotherapy was introduced by Leonard Noon 100 years ago and is the only disease-modifying treatment for allergic individuals (Allergy, 2012).

The 100-year-old treatment

Allergen immunotherapy (SCIT) has been a treatment option for allergic rhinitis, allergic asthma, and venom allergy for the last 100 years. During the first 75 years, conventional subcutaneous immunotherapy (SCIT) did not change much. However, the last 25 years has seen a growth in the development of alternatives to subcutaneous immunotherapy.



Mechanisms of allergen-specific immunotherapy (click to enlarge the image). CD27 expression on allergen-specific T cells may be a new surrogate for successful allergen-specific immunotherapy (JACI, 2012).

Omalizumab

The addition of omalizumab (trade name Xolair), an anti-IgE mAb, to immunotherapy offers the potential for increased safety and efficacy - for example, transition to SCIT in patients with difficult to control asthma.

Toll-like receptor (TLR) agonists

Activation of the innate immune system through Toll-like receptor (TLR) agonists coupled with allergens may improve the immunologic responses.



Pathogen Recognition Receptors, TLRs. This video is from: Janeway's Immunobiology, 7th Edition Murphy, Travers, & Walport. Source: Garland Science.

Altered allergens

The use of chemically altered allergens, allergoids, recombinant allergens, and relevant T-cell epitope peptides are all approaches that have yielded positive results in research studies.

Alternative modes of delivery

Alternative modes of delivery also hold promise - sublingual immunotherapy (SLIT) is rapidly approaching mainstream use in many countries (U.S. not included, possibly due to polysensation often observed in the American patients).

Epicutaneous allergen-specific immunotherapy. Skin patches coated with allergens to treat hay fever - check the caveats too listed by WSJ and JACI, 2011. 

One thing is clear: the next century of immunotherapy will be vastly different from today's current standard of care.

References:

Future forms of immunotherapy. Casale TB, Stokes JR. J Allergy Clin Immunol. 2010 Nov 19.
Toll-like receptor (TLR)

mAb: If it ends in -mumab, it's a fully human protein, -zumab is humanized (10% mouse), -ximab is chimeric (33% mouse). ACP blog, 2012.