Abstract
Previously, we reported anticancer molecules, Fc-binding antibody-recruiting molecules (Fc-ARMs), which crosslink proteins on cancer cells with endogenous immunoglobulin Gs (IgGs) via their Fc region. The mobilized IgGs on cancer cells can accommodate natural killer cells to induce antibody-dependent cellular cytotoxicity (ADCC). Because previous Fc-ARMs utilized Fc-binding peptides, their affinity to IgGs is weak, which resulted in the limited induction capability of ADCC. Previous Fc-ARMs also unitized small molecular ligands to cancer cells, which limited their universal applicability to any cancer cells. A recent study reported that protein-based Fc-ARMs might overcome the issues associated with non-proteinous Fc-ARMs. Here, we examined the universality of a protein-based Fc-ARM by replacing its tumor-binding domain with a human epidermal growth factor receptor 2 (HER2)-specific affibody (ZHER2:342). We also examined the requirement of its Fc-binding domain affinity. We found that the Fc-ARMs accepted an affibody as a tumor-binding domain to induce ADCC. Furthermore, the required residence time of the complex between Fc-ARM and IgG was ∼102 min, which was comparable to that when monoclonal antibodies bind to their specific antigens. However, we found that the extent of ADCC induced by Fc-ARM was lower than that of conventional IgG-mediated ADCC, indicating that further enhancement of the affinity of the antibody-binding terminus and tumor-binding terminus of Fc-ARM may be needed to achieve ADCC equivalent to that of conventional IgG-mediated ADCC.