Discovery of immunopotentiatory drugs: current and future strategies

If the immune system can be considered the most highly evolved natural anti-infective therapeutic system, then it would seem to be a promising target for therapeutic manipulation. However, with the obvious exception of prophylactic vaccination (often described as the most successful of all medical public health measures), broadly applicable agents that make the immune system work better have yet to be discovered. The term drug in its widest sense is generally used to include natural and synthetic therapeutic molecules from the very small (e.g. lithium salts) to the very large (e.g. insulin, interferon, monoclonal antibodies). However, the great majority of drugs conform to a much narrower definition encompassing small organic molecules with the great advantage of oral bioavailability, plus tractability in terms of large-scale synthesis, product quality-control, formulation and stability. In the field of immunology recent advances have identified large numbers of macromolecules that regulate host-defence, and many of these produce enhancement, amplification and/or diversion of immune responses in positive, therapeutically desirable directions. However, immunology has yet to provide small oral drugs that can be used to amplify and positively regulate immunity. A host of peptides and other bio-molecules have been tested in this context [1] and some have been exploited as components of investigational adjuvants for use locally with vaccines. However, none of these have found commercial application as licensed immunopotentiatory drugs.