Local complement inhibition by selective precision-targeted therapies

Excessive complement activation represents a major pathogenic mechanism for a range of serious human diseases. Complement-inhibitory therapeutics have been approved for a number of rare and ultra-rare conditions, with several others in clinical development. The vast majority of these complement-targeted drugs act via systemic inhibition that requires high dosing with associated high cost and, in addition, carries increased risks for developing life-threatening infectious diseases. Local complement inhibition, allowing lower dosing, lower costs, and a better safety profile, therefore, represents an attractive novel strategy. Several approaches to achieve local complement inhibition, including local application and site-specific targeting, are being assessed. This review will primarily focus on the tissue-specific targeting using antibody technologies for approaches both in preclinical and clinical development, and discuss its advantages and limitations. Overall, we see great promise for an upcoming generation of targeted complement inhibitors that enable selective inhibition of complement exclusively at the site of disease.