The abscopal effect: Implications for drug discovery in autoimmunity

The emergence of novel targeted therapies and the tools that increase the stability and delivery of drugs have greatly improved treatment outcomes in autoimmune diseases (ADs). Recently-developed strategies deplete specific deleterious T- and B-cell subsets, interrupt receptor-ligand interactions, and/or inhibit the secretion or activity of inflammatory mediators linked to tissue damage. Although generally efficient, these lines of intervention have limitations, with documented cases of drug-resistance and undesired side effects. They are also difficult to apply to non-organ-specific ADs, where the trigger and effector antigens are unknown and in which autoimmune activity is widely spread throughout the body. The potential of cellular modulators that act at a distance from the affected site, by abscopal effect, as described in the case of cancer radio- and immuno-therapy might be especially efficient in the context of ADs. Future research to discover small molecule- and peptide-based treatments will need to explore potential drugs with abscopal effects that could elicit potent immune tolerance and clinical quiescence to restore quality of life of affected patients.