While some preclinical and clinical studies have explored ACC in the treatment of cancer, such as the use of anti-GD2 IL2 conjugate Hu14.18-IL2 in the treatment of neuroblastoma and melanoma (50), this study demonstrates that next-generation engineered cytokine such as Neo2/15 and a novel designed IL-2 variant HL2-KOA1 can also be conveniently and robustly conjugated to a tumor-specific antibody downstream of the CH3 domain of the constant heavy chain. Here, IL2 is linked to neoplasm.