First ADCs for solid tumors were eventually not further developed in clinical trials based on relevant off-target toxicities due to linker instability, which prevented dose-escalation thus limiting efficacy.7 Notably, off-target toxicities represent one of the main ADCs’ limitations, among others (Table 1).8 Subsequently, Sievers et al evaluated an anti-CD33 immunoconjugate, gemtuzumab ozogamicin, for the treatment of relapsed/refractory CD33+ acute myeloid leukemia in phase I and II trials. This evidence concerns the gene CD33 and acute myeloid leukemia.