In summary, informed by the expression and distribution of FcγRIIIa and FcγR-expressing cells in therapy-resistant and aggressive breast cancer subsets, we combined antibody glycoengineering and point mutation to develop antibodies with greatly enhanced affinity to FcγRIIIa, allowing engagement with immune cells without the requirement of immune complex formation. The gene discussed is FCGR2A; the disease is breast carcinoma.