A joint collaboration between researchers from Commit Biologics, Christian-Albrechts-University in Kiel and Aarhus University has led to a better understanding of the complement system. The complement system plays a vital role in immune defenses. However, it remains inherently difficult to activate and is currently underexploited in cancer treatment. The published study describes how Fc-independent recruitment of C1 by modular bispecific single-domain antibodies, termed BiCEs, can potently activate the complement system. BiCEs are superior to tested mAbs in activating complement due to a combination of their higher affinity for C1q and their higher flexibility, which both contribute to C1 engagement during antigen recognition. Medicines directing the killing function of the complement system against malignant and pathogenic cells represent an exciting new type of therapeutics to treat cancer, infectious and autoimmune diseases.