Mechanisms of immunotherapy and surrogate markers.

Understanding mechanisms of inducible antigen-specific tolerance will improve immunotherapy and reveal the most relevant biomarkers for objectively measuring response to immunotherapy in clinical trials and routine practice. Various physiological and laboratory parameters are proposed as biomarkers of an immunological response to vaccines, although their surrogacy for clinical end points is unproven. Examples of physiological biomarkers include suppression of allergen-induced early- and late-phase responses. Laboratory biomarkers include increases in bioactive allergen-specific IgG and IgA levels and T-cell interleukin (IL)-10 production. There is a continuing unmet need for biomarkers that will allow prediction of treatment efficacy and assist in monitoring the response after starting therapy or postwithdrawal.