Shifting From Systemic to Precision-Targeted Complement Therapies: Opportunities and Hurdles

Area of Science:

• Immunology
• Pharmacology
• Biomedical Engineering

Background:

• Systemic complement inhibitors have advanced treatment but present challenges like infection risk and off-target effects.
• Many complement-mediated diseases necessitate long-term management, increasing healthcare burdens.
• Targeting complement therapies to specific body compartments offers a promising avenue for precision medicine.

Purpose of the Study:

• To review approved complement therapeutics and emerging preclinical strategies.
• To highlight essential properties for targeted complement therapies, including administration routes, tissue penetration, specificity, and mechanism of action.
• To explore both dampening and localized activation strategies for complement intervention.

Main Methods:

• Review of approved complement therapeutics.
• Analysis of preclinical data on novel complement intervention concepts.
• Identification of key characteristics for targeted therapy development.

Main Results:

• Approved systemic complement inhibitors show clinical success but have limitations.
• Emerging concepts focus on organ-, tissue-, or cell-specific complement modulation.
• Key properties for targeted therapies include administration route, penetration, specificity, and mode of action.

Conclusions:

• Next-generation complement therapeutics hold significant potential for more precise and effective clinical outcomes.
• Targeted complement intervention can overcome limitations of current systemic approaches.
• Future strategies may involve both inhibiting and locally activating the complement system for therapeutic benefit.