An asymmetric heterodimeric antibody includes a knob structure formed in a CH3 domain of a first heavy chain； a hole structure formed in a CH3 domain of a second heavy chain, wherein the hole structure is configured to accommodate the knob structure so that a heterodimeric antibody is formed； and a T-cell targeting domain fused to the CH3 domain of the first heavy chain or the second heavy chain, wherein the T-cell targeting domain binds specifically to an antigen on the T-cell. The T-cell targeting domain is a ScFv or Fab derived from an anti-CD3 antibody. The asymmetric heterodimeric antibody may have L234A and L235A mutations or L235A and G237A such that its effector binding is compromised.本發明提供一種不對稱異二聚抗體，其包括：杵結構，其形成於第一重鏈之CH3域中；臼結構，其形成於第二重鏈的CH3域中，其中該臼結構經結構設計成容納該杵之結構，以利形成異二聚抗體；以及T細胞靶向域，其融合至該第一重鏈或該第二重鏈之該CH3域，其中該T細胞靶向域特異性地結合至該T細胞上之抗原。該T細胞靶向域為源於抗CD3抗體之ScFv或Fab。該不對稱異二聚抗體可具有L234A及L235A突變或L235A及G237A突變，使得其效應子結合受到減損。
