Peptide Assemblies as Active Immunotherapies to Treat Chronic Inflammatory Diseases

Chronic inflammatory diseases such as rheumatoid arthritis, psoriasis, and inflammatory bowel disease are currently treated using monoclonal antibodies and other biologics that neutralize key inflammatory mediators such as cytokines. Although beneficial for many, a large proportion of patients do not respond to them or stop responding as they develop anti-drug antibodies against the repeated injections. Anti-cytokine biologics also are expensive and have stringent storage requirements, limiting access to only the most well-resourced areas of the globe. Active immunotherapies, where therapeutic B-cell or T-cell responses are generated in the patient against selected targets, may provide alternatives with fewer dosing requirements, better shelf stability, and lower non-response rates. However, platforms for safely and predictably generating therapeutic anti-inflammatory adaptive immune responses have yet to be developed clinically. In this talk, active immunotherapies against several targets, including TNF, IL-1β, IL-17, phosphorylcholine, and complement proteins will be described, based on supramolecular peptide and protein assemblies. Design rules for eliciting predictable B-cell and T-cell responses against chosen targets using supramolecular peptide assemblies will be discussed, along with strategies for raising therapeutic responses in tissues of interest, including the gut. In preclinical mouse models of psoriasis, acute septic shock, inflammatory bowel disease, and rheumatoid arthritis, supramolecular active immunotherapies have exhibited considerable therapeutic efficacy, and these results will be highlighted.