Fig. 3.

Models for CD16A engagement and IgG competition. A/B In the ground state, CD16A on innate immune cells is occupied by polyclonal plasma IgG. This creates a threshold for Fc-based therapeutic antibodies or immuno-engagers, employing the recognition site on CD16A also bound by the Fc proportion of IgG antibodies, thus limiting therapeutic potential. C Tetravalent bispecific immuno-engagers, which recognize a different epitope on CD16A, are virtually unaffected by plasma IgG. This enables high affinity binding of CD16A and respective tumor antigens leading to strong ADCC and immuno-surveillance.