Thus, the challenge for the development of more potent FcγR effector mAbs is to overcome three major obstacles. First, improving activation potency by selectively enhancing interaction with activating‐type FcγR, particularly FcγRIIIa owing to its predominant role in ADCC‐mediated killing of tumor cells. Second, reducing binding interactions with the inhibitory FcγRIIb. These two approaches improve the FcγR A‐to‐I ratio of cytotoxic IgG1 mAbs. Third, overcoming the significant affinity difference in the interaction with the main FcγRIII allelic forms of FcγRIIIa‐V158 and FcγRIIIa‐F158 76, 83, 84 which appears to be an important source of patient variability in responses to therapeutic mAb treatment of cancer.