Novel synthetic biology-based ADCC technologies are provided that enhance or enable ADCC responses, for example, through a rationally-designed soluble universal ADCC enhancer protein (SUAEP) where a high-affinity CD3-binding domain is fused to a high-affinity Fc-binding domain. The SUAEP technology can be used to prevent or treat cancers, infectious, inflammatory or autoimmune diseases, and other diseases where elimination of diseased cells is desirable.