Human epidermal growth factor receptor 2 (HER2)–Cluster of differentiation 3 (CD3) complex (HER2–CD3)

The HER2–CD3 cell–cell interface is a therapeutic target complex formed by the simultaneous binding of a bispecific agent to Human Epidermal Growth Factor Receptor 2 (HER2) on a target cell and the Cluster of Differentiation 3 (CD3) subunit of the T-cell receptor complex on a T-lymphocyte [1, 2]. HER2, also known as ERBB2, is a receptor tyrosine kinase that is frequently overexpressed or amplified in various cancers, including breast, gastric, and esophageal malignancies, where it promotes cell survival and proliferation [1, 3]. CD3 is an essential co-receptor for T-cell activation and signal transduction [2]. By bridging these two molecules, bispecific T-cell engagers (BiTEs) or bispecific antibodies (bsAbs) facilitate the formation of an artificial immunological synapse, bypassing the requirement for traditional Major Histocompatibility Complex (MHC) class I antigen presentation [4]. This interaction leads to the localized activation of T-cells, resulting in the release of perforins and granzymes that induce apoptosis in the HER2-positive tumor cell [4, 5]. Clinical development of drugs targeting this interface aims to harness the potency of the adaptive immune system against solid tumors, though it requires careful management of systemic inflammatory responses such as cytokine release syndrome [5, 6].

Other names

HER2 x CD3ERBB2-CD3HER2-T-cell engager targetHER2-CD3 bispecific target

Redirection of T-cells to HER2-expressing tumor cells, leading to the formation of an artificial immunological synapse, T-cell activation, and subsequent tumor cell lysis via perforin and granzyme release.